Combination of 5-aminosalicylic acid and hyperthermia synergistically enhances apoptotic cell death in HSC-3 cells due to intracellular nitric oxide/peroxynitrite generation
The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therap...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Moniruzzaman, Rohan [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2019transfer abstract |
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| Schlagwörter: |
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| Umfang: |
10 |
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| Übergeordnetes Werk: |
Enthalten in: GW26-e0273 Relationship between thrombelastography test and routine platelet parameters in patients with acute coronary syndrome - Hao, Lijun ELSEVIER, 2015, an international journal providing a forum for original and pertinent contributions in cancer research, Amsterdam [u.a.] |
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| Übergeordnetes Werk: |
volume:451 ; year:2019 ; day:1 ; month:06 ; pages:58-67 ; extent:10 |
| Links: |
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| DOI / URN: |
10.1016/j.canlet.2019.03.004 |
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ELV046259481 |
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| 245 | 1 | 0 | |a Combination of 5-aminosalicylic acid and hyperthermia synergistically enhances apoptotic cell death in HSC-3 cells due to intracellular nitric oxide/peroxynitrite generation |
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| 520 | |a The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. | ||
| 520 | |a The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. | ||
| 650 | 7 | |a OSCC |2 Elsevier | |
| 650 | 7 | |a Reactive oxygen and nitrogen species |2 Elsevier | |
| 650 | 7 | |a Drug repurposing |2 Elsevier | |
| 650 | 7 | |a Cancer cell death |2 Elsevier | |
| 700 | 1 | |a Rehman, Mati Ur |4 oth | |
| 700 | 1 | |a Zhao, Qing-Li |4 oth | |
| 700 | 1 | |a Jawaid, Paras |4 oth | |
| 700 | 1 | |a Mitsuhashi, Yohei |4 oth | |
| 700 | 1 | |a Sakurai, Kotaro |4 oth | |
| 700 | 1 | |a Heshiki, Wataru |4 oth | |
| 700 | 1 | |a Ogawa, Ryohei |4 oth | |
| 700 | 1 | |a Tomihara, Kei |4 oth | |
| 700 | 1 | |a Saitoh, Jun-ichi |4 oth | |
| 700 | 1 | |a Noguchi, Kyo |4 oth | |
| 700 | 1 | |a Kondo, Takashi |4 oth | |
| 700 | 1 | |a Noguchi, Makoto |4 oth | |
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10.1016/j.canlet.2019.03.004 doi GBV00000000000566.pica (DE-627)ELV046259481 (ELSEVIER)S0304-3835(19)30147-8 DE-627 ger DE-627 rakwb eng 610 VZ 600 690 VZ 51.00 bkl 51.32 bkl Moniruzzaman, Rohan verfasserin aut Combination of 5-aminosalicylic acid and hyperthermia synergistically enhances apoptotic cell death in HSC-3 cells due to intracellular nitric oxide/peroxynitrite generation 2019transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. OSCC Elsevier Reactive oxygen and nitrogen species Elsevier Drug repurposing Elsevier Cancer cell death Elsevier Rehman, Mati Ur oth Zhao, Qing-Li oth Jawaid, Paras oth Mitsuhashi, Yohei oth Sakurai, Kotaro oth Heshiki, Wataru oth Ogawa, Ryohei oth Tomihara, Kei oth Saitoh, Jun-ichi oth Noguchi, Kyo oth Kondo, Takashi oth Noguchi, Makoto oth Enthalten in Elsevier Science Hao, Lijun ELSEVIER GW26-e0273 Relationship between thrombelastography test and routine platelet parameters in patients with acute coronary syndrome 2015 an international journal providing a forum for original and pertinent contributions in cancer research Amsterdam [u.a.] (DE-627)ELV013094742 volume:451 year:2019 day:1 month:06 pages:58-67 extent:10 https://doi.org/10.1016/j.canlet.2019.03.004 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_11 GBV_ILN_40 51.00 Werkstoffkunde: Allgemeines VZ 51.32 Werkstoffmechanik VZ AR 451 2019 1 0601 58-67 10 |
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10.1016/j.canlet.2019.03.004 doi GBV00000000000566.pica (DE-627)ELV046259481 (ELSEVIER)S0304-3835(19)30147-8 DE-627 ger DE-627 rakwb eng 610 VZ 600 690 VZ 51.00 bkl 51.32 bkl Moniruzzaman, Rohan verfasserin aut Combination of 5-aminosalicylic acid and hyperthermia synergistically enhances apoptotic cell death in HSC-3 cells due to intracellular nitric oxide/peroxynitrite generation 2019transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. OSCC Elsevier Reactive oxygen and nitrogen species Elsevier Drug repurposing Elsevier Cancer cell death Elsevier Rehman, Mati Ur oth Zhao, Qing-Li oth Jawaid, Paras oth Mitsuhashi, Yohei oth Sakurai, Kotaro oth Heshiki, Wataru oth Ogawa, Ryohei oth Tomihara, Kei oth Saitoh, Jun-ichi oth Noguchi, Kyo oth Kondo, Takashi oth Noguchi, Makoto oth Enthalten in Elsevier Science Hao, Lijun ELSEVIER GW26-e0273 Relationship between thrombelastography test and routine platelet parameters in patients with acute coronary syndrome 2015 an international journal providing a forum for original and pertinent contributions in cancer research Amsterdam [u.a.] (DE-627)ELV013094742 volume:451 year:2019 day:1 month:06 pages:58-67 extent:10 https://doi.org/10.1016/j.canlet.2019.03.004 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_11 GBV_ILN_40 51.00 Werkstoffkunde: Allgemeines VZ 51.32 Werkstoffmechanik VZ AR 451 2019 1 0601 58-67 10 |
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10.1016/j.canlet.2019.03.004 doi GBV00000000000566.pica (DE-627)ELV046259481 (ELSEVIER)S0304-3835(19)30147-8 DE-627 ger DE-627 rakwb eng 610 VZ 600 690 VZ 51.00 bkl 51.32 bkl Moniruzzaman, Rohan verfasserin aut Combination of 5-aminosalicylic acid and hyperthermia synergistically enhances apoptotic cell death in HSC-3 cells due to intracellular nitric oxide/peroxynitrite generation 2019transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. OSCC Elsevier Reactive oxygen and nitrogen species Elsevier Drug repurposing Elsevier Cancer cell death Elsevier Rehman, Mati Ur oth Zhao, Qing-Li oth Jawaid, Paras oth Mitsuhashi, Yohei oth Sakurai, Kotaro oth Heshiki, Wataru oth Ogawa, Ryohei oth Tomihara, Kei oth Saitoh, Jun-ichi oth Noguchi, Kyo oth Kondo, Takashi oth Noguchi, Makoto oth Enthalten in Elsevier Science Hao, Lijun ELSEVIER GW26-e0273 Relationship between thrombelastography test and routine platelet parameters in patients with acute coronary syndrome 2015 an international journal providing a forum for original and pertinent contributions in cancer research Amsterdam [u.a.] (DE-627)ELV013094742 volume:451 year:2019 day:1 month:06 pages:58-67 extent:10 https://doi.org/10.1016/j.canlet.2019.03.004 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_11 GBV_ILN_40 51.00 Werkstoffkunde: Allgemeines VZ 51.32 Werkstoffmechanik VZ AR 451 2019 1 0601 58-67 10 |
| allfieldsGer |
10.1016/j.canlet.2019.03.004 doi GBV00000000000566.pica (DE-627)ELV046259481 (ELSEVIER)S0304-3835(19)30147-8 DE-627 ger DE-627 rakwb eng 610 VZ 600 690 VZ 51.00 bkl 51.32 bkl Moniruzzaman, Rohan verfasserin aut Combination of 5-aminosalicylic acid and hyperthermia synergistically enhances apoptotic cell death in HSC-3 cells due to intracellular nitric oxide/peroxynitrite generation 2019transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. OSCC Elsevier Reactive oxygen and nitrogen species Elsevier Drug repurposing Elsevier Cancer cell death Elsevier Rehman, Mati Ur oth Zhao, Qing-Li oth Jawaid, Paras oth Mitsuhashi, Yohei oth Sakurai, Kotaro oth Heshiki, Wataru oth Ogawa, Ryohei oth Tomihara, Kei oth Saitoh, Jun-ichi oth Noguchi, Kyo oth Kondo, Takashi oth Noguchi, Makoto oth Enthalten in Elsevier Science Hao, Lijun ELSEVIER GW26-e0273 Relationship between thrombelastography test and routine platelet parameters in patients with acute coronary syndrome 2015 an international journal providing a forum for original and pertinent contributions in cancer research Amsterdam [u.a.] (DE-627)ELV013094742 volume:451 year:2019 day:1 month:06 pages:58-67 extent:10 https://doi.org/10.1016/j.canlet.2019.03.004 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_11 GBV_ILN_40 51.00 Werkstoffkunde: Allgemeines VZ 51.32 Werkstoffmechanik VZ AR 451 2019 1 0601 58-67 10 |
| allfieldsSound |
10.1016/j.canlet.2019.03.004 doi GBV00000000000566.pica (DE-627)ELV046259481 (ELSEVIER)S0304-3835(19)30147-8 DE-627 ger DE-627 rakwb eng 610 VZ 600 690 VZ 51.00 bkl 51.32 bkl Moniruzzaman, Rohan verfasserin aut Combination of 5-aminosalicylic acid and hyperthermia synergistically enhances apoptotic cell death in HSC-3 cells due to intracellular nitric oxide/peroxynitrite generation 2019transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. OSCC Elsevier Reactive oxygen and nitrogen species Elsevier Drug repurposing Elsevier Cancer cell death Elsevier Rehman, Mati Ur oth Zhao, Qing-Li oth Jawaid, Paras oth Mitsuhashi, Yohei oth Sakurai, Kotaro oth Heshiki, Wataru oth Ogawa, Ryohei oth Tomihara, Kei oth Saitoh, Jun-ichi oth Noguchi, Kyo oth Kondo, Takashi oth Noguchi, Makoto oth Enthalten in Elsevier Science Hao, Lijun ELSEVIER GW26-e0273 Relationship between thrombelastography test and routine platelet parameters in patients with acute coronary syndrome 2015 an international journal providing a forum for original and pertinent contributions in cancer research Amsterdam [u.a.] (DE-627)ELV013094742 volume:451 year:2019 day:1 month:06 pages:58-67 extent:10 https://doi.org/10.1016/j.canlet.2019.03.004 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_11 GBV_ILN_40 51.00 Werkstoffkunde: Allgemeines VZ 51.32 Werkstoffmechanik VZ AR 451 2019 1 0601 58-67 10 |
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combination of 5-aminosalicylic acid and hyperthermia synergistically enhances apoptotic cell death in hsc-3 cells due to intracellular nitric oxide/peroxynitrite generation |
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Combination of 5-aminosalicylic acid and hyperthermia synergistically enhances apoptotic cell death in HSC-3 cells due to intracellular nitric oxide/peroxynitrite generation |
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The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. |
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The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. |
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The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC. |
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These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC.</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">OSCC</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Reactive oxygen and nitrogen species</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Drug repurposing</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Cancer cell death</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rehman, Mati Ur</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhao, Qing-Li</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Jawaid, Paras</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Mitsuhashi, Yohei</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sakurai, Kotaro</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Heshiki, Wataru</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ogawa, Ryohei</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tomihara, Kei</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Saitoh, Jun-ichi</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Noguchi, Kyo</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kondo, Takashi</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Noguchi, Makoto</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier Science</subfield><subfield code="a">Hao, Lijun ELSEVIER</subfield><subfield code="t">GW26-e0273 Relationship between thrombelastography test and routine platelet parameters in patients with acute coronary syndrome</subfield><subfield code="d">2015</subfield><subfield code="d">an international journal providing a forum for original and pertinent contributions in cancer research</subfield><subfield code="g">Amsterdam [u.a.]</subfield><subfield code="w">(DE-627)ELV013094742</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:451</subfield><subfield code="g">year:2019</subfield><subfield code="g">day:1</subfield><subfield code="g">month:06</subfield><subfield code="g">pages:58-67</subfield><subfield code="g">extent:10</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.canlet.2019.03.004</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">51.00</subfield><subfield code="j">Werkstoffkunde: Allgemeines</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">51.32</subfield><subfield code="j">Werkstoffmechanik</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">451</subfield><subfield code="j">2019</subfield><subfield code="b">1</subfield><subfield code="c">0601</subfield><subfield code="h">58-67</subfield><subfield code="g">10</subfield></datafield></record></collection>
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