The FHP01 DDX3X Helicase Inhibitor Exerts Potent Anti-Tumor Activity In Vivo in Breast Cancer Pre-Clinical Models

Inhibition of DDX3X expression or activity reduces proliferation in cells from various tumor tissues, in particular in breast cancer, and its expression often correlates to tumor aggressiveness. This makes DDX3X a prominent candidate for the design of drugs for novel personalized therapeutic strateg...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Lisa Gherardini [verfasserIn] Giovanni Inzalaco [verfasserIn] Francesco Imperatore [verfasserIn] Romina D’Aurizio [verfasserIn] Lorenzo Franci [verfasserIn] Vincenzo Miragliotta [verfasserIn] Adele Boccuto [verfasserIn] Pierpaolo Calandro [verfasserIn] Matteo Andreini [verfasserIn] Alessia Tarditi [verfasserIn] Mario Chiariello [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	triple-negative breast cancer DDX3X helicase pharmacological inhibitor WNT signaling

Übergeordnetes Werk:	In: Cancers - MDPI AG, 2010, 13(2021), 19, p 4830
Übergeordnetes Werk:	volume:13 ; year:2021 ; number:19, p 4830

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cancers13194830

Katalog-ID:	DOAJ060409738

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callnumber-first	R - Medicine
author	Lisa Gherardini
spellingShingle	Lisa Gherardini misc RC254-282 misc triple-negative breast cancer misc DDX3X misc helicase misc pharmacological inhibitor misc WNT signaling misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens The FHP01 DDX3X Helicase Inhibitor Exerts Potent Anti-Tumor Activity In Vivo in Breast Cancer Pre-Clinical Models
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topic_title	RC254-282 The FHP01 DDX3X Helicase Inhibitor Exerts Potent Anti-Tumor Activity In Vivo in Breast Cancer Pre-Clinical Models triple-negative breast cancer DDX3X helicase pharmacological inhibitor WNT signaling
topic	misc RC254-282 misc triple-negative breast cancer misc DDX3X misc helicase misc pharmacological inhibitor misc WNT signaling misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc triple-negative breast cancer misc DDX3X misc helicase misc pharmacological inhibitor misc WNT signaling misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc triple-negative breast cancer misc DDX3X misc helicase misc pharmacological inhibitor misc WNT signaling misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	The FHP01 DDX3X Helicase Inhibitor Exerts Potent Anti-Tumor Activity In Vivo in Breast Cancer Pre-Clinical Models
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title_full	The FHP01 DDX3X Helicase Inhibitor Exerts Potent Anti-Tumor Activity In Vivo in Breast Cancer Pre-Clinical Models
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author_browse	Lisa Gherardini Giovanni Inzalaco Francesco Imperatore Romina D’Aurizio Lorenzo Franci Vincenzo Miragliotta Adele Boccuto Pierpaolo Calandro Matteo Andreini Alessia Tarditi Mario Chiariello
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title_sort	fhp01 ddx3x helicase inhibitor exerts potent anti-tumor activity in vivo in breast cancer pre-clinical models
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title_auth	The FHP01 DDX3X Helicase Inhibitor Exerts Potent Anti-Tumor Activity In Vivo in Breast Cancer Pre-Clinical Models
abstract	Inhibition of DDX3X expression or activity reduces proliferation in cells from various tumor tissues, in particular in breast cancer, and its expression often correlates to tumor aggressiveness. This makes DDX3X a prominent candidate for the design of drugs for novel personalized therapeutic strategies. Starting from an in silico drug discovery approach, a group of molecules has been selected by molecular docking at the RNA binding site of DDX3X. Here, the most promising among them, FHP01, was evaluated in breast cancer preclinical models. Specifically, FHP01 exhibited very effective antiproliferative and killing activity against different breast cancer cell types, among which those from triple-negative breast cancer (TNBC). Interestingly, FHP01 also inhibited WNT signaling, a key tumorigenic pathway already correlated to DDX3X functions in breast cancer model cell lines. Ultimately, FHP01 also caused a significant reduction, in vivo, in the growth of MDA MB 231-derived TNBC xenograft models. Importantly, FHP01 showed good bioavailability and no toxicity on normal peripheral blood mononuclear cells in vitro and on several mouse tissues in vivo. Overall, our data suggest that the use of FHP01 and its related compounds may represent a novel therapeutic approach with high potential against breast cancer, including the triple-negative subtype usually correlated to the most unfavorable outcomes because of the lack of available targeted therapies.
abstractGer	Inhibition of DDX3X expression or activity reduces proliferation in cells from various tumor tissues, in particular in breast cancer, and its expression often correlates to tumor aggressiveness. This makes DDX3X a prominent candidate for the design of drugs for novel personalized therapeutic strategies. Starting from an in silico drug discovery approach, a group of molecules has been selected by molecular docking at the RNA binding site of DDX3X. Here, the most promising among them, FHP01, was evaluated in breast cancer preclinical models. Specifically, FHP01 exhibited very effective antiproliferative and killing activity against different breast cancer cell types, among which those from triple-negative breast cancer (TNBC). Interestingly, FHP01 also inhibited WNT signaling, a key tumorigenic pathway already correlated to DDX3X functions in breast cancer model cell lines. Ultimately, FHP01 also caused a significant reduction, in vivo, in the growth of MDA MB 231-derived TNBC xenograft models. Importantly, FHP01 showed good bioavailability and no toxicity on normal peripheral blood mononuclear cells in vitro and on several mouse tissues in vivo. Overall, our data suggest that the use of FHP01 and its related compounds may represent a novel therapeutic approach with high potential against breast cancer, including the triple-negative subtype usually correlated to the most unfavorable outcomes because of the lack of available targeted therapies.
abstract_unstemmed	Inhibition of DDX3X expression or activity reduces proliferation in cells from various tumor tissues, in particular in breast cancer, and its expression often correlates to tumor aggressiveness. This makes DDX3X a prominent candidate for the design of drugs for novel personalized therapeutic strategies. Starting from an in silico drug discovery approach, a group of molecules has been selected by molecular docking at the RNA binding site of DDX3X. Here, the most promising among them, FHP01, was evaluated in breast cancer preclinical models. Specifically, FHP01 exhibited very effective antiproliferative and killing activity against different breast cancer cell types, among which those from triple-negative breast cancer (TNBC). Interestingly, FHP01 also inhibited WNT signaling, a key tumorigenic pathway already correlated to DDX3X functions in breast cancer model cell lines. Ultimately, FHP01 also caused a significant reduction, in vivo, in the growth of MDA MB 231-derived TNBC xenograft models. Importantly, FHP01 showed good bioavailability and no toxicity on normal peripheral blood mononuclear cells in vitro and on several mouse tissues in vivo. Overall, our data suggest that the use of FHP01 and its related compounds may represent a novel therapeutic approach with high potential against breast cancer, including the triple-negative subtype usually correlated to the most unfavorable outcomes because of the lack of available targeted therapies.
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title_short	The FHP01 DDX3X Helicase Inhibitor Exerts Potent Anti-Tumor Activity In Vivo in Breast Cancer Pre-Clinical Models
url	https://doi.org/10.3390/cancers13194830 https://doaj.org/article/2ca82ba15be04d8e90a0bd069510cf48 https://www.mdpi.com/2072-6694/13/19/4830 https://doaj.org/toc/2072-6694
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The FHP01 DDX3X Helicase Inhibitor Exerts Potent Anti-Tumor Activity In Vivo in Breast Cancer Pre-Clinical Models

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