Extracellular vesicles of cannabis with high CBD content induce anticancer signaling in human hepatocellular carcinoma
Plant-derived extracellular vesicles (EVs) have been the topic of interest in recent years due to their proven therapeutic properties. Intact or manipulated plant EVs have shown antioxidant, anti-inflammatory, and anti-cancerous activities as a result of containing bioactive metabolites and other en...
Ausführliche Beschreibung
Autor*in: |
Tahereh Tajik [verfasserIn] Kaveh Baghaei [verfasserIn] Vahid Erfani Moghadam [verfasserIn] Naser Farrokhi [verfasserIn] Seyed Alireza Salami [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2022 |
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Schlagwörter: |
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Übergeordnetes Werk: |
In: Biomedicine & Pharmacotherapy - Elsevier, 2021, 152(2022), Seite 113209- |
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Übergeordnetes Werk: |
volume:152 ; year:2022 ; pages:113209- |
Links: |
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DOI / URN: |
10.1016/j.biopha.2022.113209 |
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Katalog-ID: |
DOAJ04168849X |
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10.1016/j.biopha.2022.113209 doi (DE-627)DOAJ04168849X (DE-599)DOAJae77e45e82ea42c29f9e35619076cf09 DE-627 ger DE-627 rakwb eng RM1-950 Tahereh Tajik verfasserin aut Extracellular vesicles of cannabis with high CBD content induce anticancer signaling in human hepatocellular carcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Plant-derived extracellular vesicles (EVs) have been the topic of interest in recent years due to their proven therapeutic properties. Intact or manipulated plant EVs have shown antioxidant, anti-inflammatory, and anti-cancerous activities as a result of containing bioactive metabolites and other endogenous molecules. Less is known about the EV efficacy with high levels of bioactive secondary metabolites derived from medicinal or non-edible plants. Numerous data suggest the functionality of Cannabis sativa extract and its phytocannabinoids in cancer treatment. Here, two chemotypes of cannabis with different levels of D-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) were selected. EVs were isolated from each chemotype via differential ultracentrifugation. HPLC analysis was illustrative of the absence of THC in EVs derived from both plants. Therefore, two types of EVs were classified according to their CBD content into high- (H.C-EVs) and low-CBD EVs (L.C-EVs). Electron microscopy and DLS showed both cannabis-derived EVs (CDEVs) can be considered as exosome-like nanovesicles. Cytotoxicity assay showed that H.C-EVs strongly decreased the viability of two hepatocellular carcinoma (HCC) cell lines, HepG2 and Huh-7, in a dose and time-dependent manner compared with L.C-EVs. H.C-EVs had no significant effect on HUVECs normal cell growth. The finding showed that the H.C-EVs arrested the G0/G1 phase in the cell cycle and significantly induced cell death by activating mitochondrial-dependent apoptosis signaling pathways in both HCC cell lines. Altogether, the current study highlights that CDEVs can be an ideal natural vehicle for bioactive phytocannabinoids and a promising strategy in cancer management. Apoptosis Cannabidiol Phytocannabinoids Cell cycle arrest Extracellular vesicles Therapeutics. Pharmacology Kaveh Baghaei verfasserin aut Vahid Erfani Moghadam verfasserin aut Naser Farrokhi verfasserin aut Seyed Alireza Salami verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 152(2022), Seite 113209- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:152 year:2022 pages:113209- https://doi.org/10.1016/j.biopha.2022.113209 kostenfrei https://doaj.org/article/ae77e45e82ea42c29f9e35619076cf09 kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332222005984 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 152 2022 113209- |
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10.1016/j.biopha.2022.113209 doi (DE-627)DOAJ04168849X (DE-599)DOAJae77e45e82ea42c29f9e35619076cf09 DE-627 ger DE-627 rakwb eng RM1-950 Tahereh Tajik verfasserin aut Extracellular vesicles of cannabis with high CBD content induce anticancer signaling in human hepatocellular carcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Plant-derived extracellular vesicles (EVs) have been the topic of interest in recent years due to their proven therapeutic properties. Intact or manipulated plant EVs have shown antioxidant, anti-inflammatory, and anti-cancerous activities as a result of containing bioactive metabolites and other endogenous molecules. Less is known about the EV efficacy with high levels of bioactive secondary metabolites derived from medicinal or non-edible plants. Numerous data suggest the functionality of Cannabis sativa extract and its phytocannabinoids in cancer treatment. Here, two chemotypes of cannabis with different levels of D-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) were selected. EVs were isolated from each chemotype via differential ultracentrifugation. HPLC analysis was illustrative of the absence of THC in EVs derived from both plants. Therefore, two types of EVs were classified according to their CBD content into high- (H.C-EVs) and low-CBD EVs (L.C-EVs). Electron microscopy and DLS showed both cannabis-derived EVs (CDEVs) can be considered as exosome-like nanovesicles. Cytotoxicity assay showed that H.C-EVs strongly decreased the viability of two hepatocellular carcinoma (HCC) cell lines, HepG2 and Huh-7, in a dose and time-dependent manner compared with L.C-EVs. H.C-EVs had no significant effect on HUVECs normal cell growth. The finding showed that the H.C-EVs arrested the G0/G1 phase in the cell cycle and significantly induced cell death by activating mitochondrial-dependent apoptosis signaling pathways in both HCC cell lines. Altogether, the current study highlights that CDEVs can be an ideal natural vehicle for bioactive phytocannabinoids and a promising strategy in cancer management. Apoptosis Cannabidiol Phytocannabinoids Cell cycle arrest Extracellular vesicles Therapeutics. Pharmacology Kaveh Baghaei verfasserin aut Vahid Erfani Moghadam verfasserin aut Naser Farrokhi verfasserin aut Seyed Alireza Salami verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 152(2022), Seite 113209- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:152 year:2022 pages:113209- https://doi.org/10.1016/j.biopha.2022.113209 kostenfrei https://doaj.org/article/ae77e45e82ea42c29f9e35619076cf09 kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332222005984 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 152 2022 113209- |
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10.1016/j.biopha.2022.113209 doi (DE-627)DOAJ04168849X (DE-599)DOAJae77e45e82ea42c29f9e35619076cf09 DE-627 ger DE-627 rakwb eng RM1-950 Tahereh Tajik verfasserin aut Extracellular vesicles of cannabis with high CBD content induce anticancer signaling in human hepatocellular carcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Plant-derived extracellular vesicles (EVs) have been the topic of interest in recent years due to their proven therapeutic properties. Intact or manipulated plant EVs have shown antioxidant, anti-inflammatory, and anti-cancerous activities as a result of containing bioactive metabolites and other endogenous molecules. Less is known about the EV efficacy with high levels of bioactive secondary metabolites derived from medicinal or non-edible plants. Numerous data suggest the functionality of Cannabis sativa extract and its phytocannabinoids in cancer treatment. Here, two chemotypes of cannabis with different levels of D-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) were selected. EVs were isolated from each chemotype via differential ultracentrifugation. HPLC analysis was illustrative of the absence of THC in EVs derived from both plants. Therefore, two types of EVs were classified according to their CBD content into high- (H.C-EVs) and low-CBD EVs (L.C-EVs). Electron microscopy and DLS showed both cannabis-derived EVs (CDEVs) can be considered as exosome-like nanovesicles. Cytotoxicity assay showed that H.C-EVs strongly decreased the viability of two hepatocellular carcinoma (HCC) cell lines, HepG2 and Huh-7, in a dose and time-dependent manner compared with L.C-EVs. H.C-EVs had no significant effect on HUVECs normal cell growth. The finding showed that the H.C-EVs arrested the G0/G1 phase in the cell cycle and significantly induced cell death by activating mitochondrial-dependent apoptosis signaling pathways in both HCC cell lines. Altogether, the current study highlights that CDEVs can be an ideal natural vehicle for bioactive phytocannabinoids and a promising strategy in cancer management. Apoptosis Cannabidiol Phytocannabinoids Cell cycle arrest Extracellular vesicles Therapeutics. Pharmacology Kaveh Baghaei verfasserin aut Vahid Erfani Moghadam verfasserin aut Naser Farrokhi verfasserin aut Seyed Alireza Salami verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 152(2022), Seite 113209- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:152 year:2022 pages:113209- https://doi.org/10.1016/j.biopha.2022.113209 kostenfrei https://doaj.org/article/ae77e45e82ea42c29f9e35619076cf09 kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332222005984 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 152 2022 113209- |
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10.1016/j.biopha.2022.113209 doi (DE-627)DOAJ04168849X (DE-599)DOAJae77e45e82ea42c29f9e35619076cf09 DE-627 ger DE-627 rakwb eng RM1-950 Tahereh Tajik verfasserin aut Extracellular vesicles of cannabis with high CBD content induce anticancer signaling in human hepatocellular carcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Plant-derived extracellular vesicles (EVs) have been the topic of interest in recent years due to their proven therapeutic properties. Intact or manipulated plant EVs have shown antioxidant, anti-inflammatory, and anti-cancerous activities as a result of containing bioactive metabolites and other endogenous molecules. Less is known about the EV efficacy with high levels of bioactive secondary metabolites derived from medicinal or non-edible plants. Numerous data suggest the functionality of Cannabis sativa extract and its phytocannabinoids in cancer treatment. Here, two chemotypes of cannabis with different levels of D-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) were selected. EVs were isolated from each chemotype via differential ultracentrifugation. HPLC analysis was illustrative of the absence of THC in EVs derived from both plants. Therefore, two types of EVs were classified according to their CBD content into high- (H.C-EVs) and low-CBD EVs (L.C-EVs). Electron microscopy and DLS showed both cannabis-derived EVs (CDEVs) can be considered as exosome-like nanovesicles. Cytotoxicity assay showed that H.C-EVs strongly decreased the viability of two hepatocellular carcinoma (HCC) cell lines, HepG2 and Huh-7, in a dose and time-dependent manner compared with L.C-EVs. H.C-EVs had no significant effect on HUVECs normal cell growth. The finding showed that the H.C-EVs arrested the G0/G1 phase in the cell cycle and significantly induced cell death by activating mitochondrial-dependent apoptosis signaling pathways in both HCC cell lines. Altogether, the current study highlights that CDEVs can be an ideal natural vehicle for bioactive phytocannabinoids and a promising strategy in cancer management. Apoptosis Cannabidiol Phytocannabinoids Cell cycle arrest Extracellular vesicles Therapeutics. Pharmacology Kaveh Baghaei verfasserin aut Vahid Erfani Moghadam verfasserin aut Naser Farrokhi verfasserin aut Seyed Alireza Salami verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 152(2022), Seite 113209- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:152 year:2022 pages:113209- https://doi.org/10.1016/j.biopha.2022.113209 kostenfrei https://doaj.org/article/ae77e45e82ea42c29f9e35619076cf09 kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332222005984 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 152 2022 113209- |
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extracellular vesicles of cannabis with high cbd content induce anticancer signaling in human hepatocellular carcinoma |
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Extracellular vesicles of cannabis with high CBD content induce anticancer signaling in human hepatocellular carcinoma |
abstract |
Plant-derived extracellular vesicles (EVs) have been the topic of interest in recent years due to their proven therapeutic properties. Intact or manipulated plant EVs have shown antioxidant, anti-inflammatory, and anti-cancerous activities as a result of containing bioactive metabolites and other endogenous molecules. Less is known about the EV efficacy with high levels of bioactive secondary metabolites derived from medicinal or non-edible plants. Numerous data suggest the functionality of Cannabis sativa extract and its phytocannabinoids in cancer treatment. Here, two chemotypes of cannabis with different levels of D-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) were selected. EVs were isolated from each chemotype via differential ultracentrifugation. HPLC analysis was illustrative of the absence of THC in EVs derived from both plants. Therefore, two types of EVs were classified according to their CBD content into high- (H.C-EVs) and low-CBD EVs (L.C-EVs). Electron microscopy and DLS showed both cannabis-derived EVs (CDEVs) can be considered as exosome-like nanovesicles. Cytotoxicity assay showed that H.C-EVs strongly decreased the viability of two hepatocellular carcinoma (HCC) cell lines, HepG2 and Huh-7, in a dose and time-dependent manner compared with L.C-EVs. H.C-EVs had no significant effect on HUVECs normal cell growth. The finding showed that the H.C-EVs arrested the G0/G1 phase in the cell cycle and significantly induced cell death by activating mitochondrial-dependent apoptosis signaling pathways in both HCC cell lines. Altogether, the current study highlights that CDEVs can be an ideal natural vehicle for bioactive phytocannabinoids and a promising strategy in cancer management. |
abstractGer |
Plant-derived extracellular vesicles (EVs) have been the topic of interest in recent years due to their proven therapeutic properties. Intact or manipulated plant EVs have shown antioxidant, anti-inflammatory, and anti-cancerous activities as a result of containing bioactive metabolites and other endogenous molecules. Less is known about the EV efficacy with high levels of bioactive secondary metabolites derived from medicinal or non-edible plants. Numerous data suggest the functionality of Cannabis sativa extract and its phytocannabinoids in cancer treatment. Here, two chemotypes of cannabis with different levels of D-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) were selected. EVs were isolated from each chemotype via differential ultracentrifugation. HPLC analysis was illustrative of the absence of THC in EVs derived from both plants. Therefore, two types of EVs were classified according to their CBD content into high- (H.C-EVs) and low-CBD EVs (L.C-EVs). Electron microscopy and DLS showed both cannabis-derived EVs (CDEVs) can be considered as exosome-like nanovesicles. Cytotoxicity assay showed that H.C-EVs strongly decreased the viability of two hepatocellular carcinoma (HCC) cell lines, HepG2 and Huh-7, in a dose and time-dependent manner compared with L.C-EVs. H.C-EVs had no significant effect on HUVECs normal cell growth. The finding showed that the H.C-EVs arrested the G0/G1 phase in the cell cycle and significantly induced cell death by activating mitochondrial-dependent apoptosis signaling pathways in both HCC cell lines. Altogether, the current study highlights that CDEVs can be an ideal natural vehicle for bioactive phytocannabinoids and a promising strategy in cancer management. |
abstract_unstemmed |
Plant-derived extracellular vesicles (EVs) have been the topic of interest in recent years due to their proven therapeutic properties. Intact or manipulated plant EVs have shown antioxidant, anti-inflammatory, and anti-cancerous activities as a result of containing bioactive metabolites and other endogenous molecules. Less is known about the EV efficacy with high levels of bioactive secondary metabolites derived from medicinal or non-edible plants. Numerous data suggest the functionality of Cannabis sativa extract and its phytocannabinoids in cancer treatment. Here, two chemotypes of cannabis with different levels of D-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) were selected. EVs were isolated from each chemotype via differential ultracentrifugation. HPLC analysis was illustrative of the absence of THC in EVs derived from both plants. Therefore, two types of EVs were classified according to their CBD content into high- (H.C-EVs) and low-CBD EVs (L.C-EVs). Electron microscopy and DLS showed both cannabis-derived EVs (CDEVs) can be considered as exosome-like nanovesicles. Cytotoxicity assay showed that H.C-EVs strongly decreased the viability of two hepatocellular carcinoma (HCC) cell lines, HepG2 and Huh-7, in a dose and time-dependent manner compared with L.C-EVs. H.C-EVs had no significant effect on HUVECs normal cell growth. The finding showed that the H.C-EVs arrested the G0/G1 phase in the cell cycle and significantly induced cell death by activating mitochondrial-dependent apoptosis signaling pathways in both HCC cell lines. Altogether, the current study highlights that CDEVs can be an ideal natural vehicle for bioactive phytocannabinoids and a promising strategy in cancer management. |
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title_short |
Extracellular vesicles of cannabis with high CBD content induce anticancer signaling in human hepatocellular carcinoma |
url |
https://doi.org/10.1016/j.biopha.2022.113209 https://doaj.org/article/ae77e45e82ea42c29f9e35619076cf09 http://www.sciencedirect.com/science/article/pii/S0753332222005984 https://doaj.org/toc/0753-3322 |
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Kaveh Baghaei Vahid Erfani Moghadam Naser Farrokhi Seyed Alireza Salami |
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