The synthetic retinoid ST1926 attenuates prostate cancer growth and potentially targets prostate cancer stem-like cells

Hisham F Bahmad, Houda Samman, Alissar Monzer, Ola Hadadeh, Katia Cheaito, Rana Abdel-Samad, Berthe Hayar, Claudio Pisano, Hiba Msheik, Yen-Nien Liu, Nadine Darwiche, Wassim Abou-Kheir

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

Retinoids are vitamin A derivatives that regulate crucial biological processes such as cellular proliferation, apoptosis, and differentiation. The use of natural retinoids in cancer therapy is limited due to their toxicity and the acquired resistance by cancer cells. Therefore, synthetic retinoids were developed, such as the atypical adamantyl retinoid ST1926 that provides enhanced bioavailability and reduced toxicity. We have assessed the in vitro and in vivo antitumor properties and mechanism of action of ST1926 in targeting cancer stem-like cells population of human prostate cancer (PCa) cell lines, DU145 and PC3, and mouse PCa cell lines, PLum-AD and PLum-AI. We demonstrated that ST1926 substantially reduced proliferation of PCa cells and induced cell cycle arrest, p53-independent apoptosis, and early DNA damage. It also decreased migration and invasion of PCa cells and significantly reduced prostate spheres formation ability in vitro denoting sufficient eradication of the self-renewal ability of the highly androgen-resistant cancer stem cells. Importantly, ST1926 potently inhibited PCa tumor growth and progression in vivo. Our results highlight the potential of ST1926 in PCa therapy and warrant its clinical development.

原文英語
頁(從 - 到)1208-1220
頁數13
期刊Molecular Carcinogenesis
58
發行號7
DOIs
出版狀態已發佈 - 七月 2019

指紋

Neoplastic Stem Cells
Retinoids
Prostatic Neoplasms
Growth
Apoptosis
Biological Phenomena
Cell Line
Neoplasms
Cell Cycle Checkpoints
Vitamin A
Biological Availability
Androgens
DNA Damage
3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid
Prostate
Cell Proliferation
Therapeutics
Population

引用此文

Bahmad, H. F., Samman, H., Monzer, A., Hadadeh, O., Cheaito, K., Abdel-Samad, R., ... Abou-Kheir, W. (2019). The synthetic retinoid ST1926 attenuates prostate cancer growth and potentially targets prostate cancer stem-like cells. Molecular Carcinogenesis, 58(7), 1208-1220. https://doi.org/10.1002/mc.23004

The synthetic retinoid ST1926 attenuates prostate cancer growth and potentially targets prostate cancer stem-like cells. / Bahmad, Hisham F; Samman, Houda; Monzer, Alissar; Hadadeh, Ola; Cheaito, Katia; Abdel-Samad, Rana; Hayar, Berthe; Pisano, Claudio; Msheik, Hiba; Liu, Yen-Nien; Darwiche, Nadine; Abou-Kheir, Wassim.

於: Molecular Carcinogenesis, 卷 58, 編號 7, 07.2019, p. 1208-1220.

研究成果: 雜誌貢獻文章

Bahmad, HF, Samman, H, Monzer, A, Hadadeh, O, Cheaito, K, Abdel-Samad, R, Hayar, B, Pisano, C, Msheik, H, Liu, Y-N, Darwiche, N & Abou-Kheir, W 2019, 'The synthetic retinoid ST1926 attenuates prostate cancer growth and potentially targets prostate cancer stem-like cells', Molecular Carcinogenesis, 卷 58, 編號 7, 頁 1208-1220. https://doi.org/10.1002/mc.23004
Bahmad, Hisham F ; Samman, Houda ; Monzer, Alissar ; Hadadeh, Ola ; Cheaito, Katia ; Abdel-Samad, Rana ; Hayar, Berthe ; Pisano, Claudio ; Msheik, Hiba ; Liu, Yen-Nien ; Darwiche, Nadine ; Abou-Kheir, Wassim. / The synthetic retinoid ST1926 attenuates prostate cancer growth and potentially targets prostate cancer stem-like cells. 於: Molecular Carcinogenesis. 2019 ; 卷 58, 編號 7. 頁 1208-1220.
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abstract = "Retinoids are vitamin A derivatives that regulate crucial biological processes such as cellular proliferation, apoptosis, and differentiation. The use of natural retinoids in cancer therapy is limited due to their toxicity and the acquired resistance by cancer cells. Therefore, synthetic retinoids were developed, such as the atypical adamantyl retinoid ST1926 that provides enhanced bioavailability and reduced toxicity. We have assessed the in vitro and in vivo antitumor properties and mechanism of action of ST1926 in targeting cancer stem-like cells population of human prostate cancer (PCa) cell lines, DU145 and PC3, and mouse PCa cell lines, PLum-AD and PLum-AI. We demonstrated that ST1926 substantially reduced proliferation of PCa cells and induced cell cycle arrest, p53-independent apoptosis, and early DNA damage. It also decreased migration and invasion of PCa cells and significantly reduced prostate spheres formation ability in vitro denoting sufficient eradication of the self-renewal ability of the highly androgen-resistant cancer stem cells. Importantly, ST1926 potently inhibited PCa tumor growth and progression in vivo. Our results highlight the potential of ST1926 in PCa therapy and warrant its clinical development.",
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AU - Bahmad, Hisham F

AU - Samman, Houda

AU - Monzer, Alissar

AU - Hadadeh, Ola

AU - Cheaito, Katia

AU - Abdel-Samad, Rana

AU - Hayar, Berthe

AU - Pisano, Claudio

AU - Msheik, Hiba

AU - Liu, Yen-Nien

AU - Darwiche, Nadine

AU - Abou-Kheir, Wassim

N1 - © 2019 Wiley Periodicals, Inc.

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N2 - Retinoids are vitamin A derivatives that regulate crucial biological processes such as cellular proliferation, apoptosis, and differentiation. The use of natural retinoids in cancer therapy is limited due to their toxicity and the acquired resistance by cancer cells. Therefore, synthetic retinoids were developed, such as the atypical adamantyl retinoid ST1926 that provides enhanced bioavailability and reduced toxicity. We have assessed the in vitro and in vivo antitumor properties and mechanism of action of ST1926 in targeting cancer stem-like cells population of human prostate cancer (PCa) cell lines, DU145 and PC3, and mouse PCa cell lines, PLum-AD and PLum-AI. We demonstrated that ST1926 substantially reduced proliferation of PCa cells and induced cell cycle arrest, p53-independent apoptosis, and early DNA damage. It also decreased migration and invasion of PCa cells and significantly reduced prostate spheres formation ability in vitro denoting sufficient eradication of the self-renewal ability of the highly androgen-resistant cancer stem cells. Importantly, ST1926 potently inhibited PCa tumor growth and progression in vivo. Our results highlight the potential of ST1926 in PCa therapy and warrant its clinical development.

AB - Retinoids are vitamin A derivatives that regulate crucial biological processes such as cellular proliferation, apoptosis, and differentiation. The use of natural retinoids in cancer therapy is limited due to their toxicity and the acquired resistance by cancer cells. Therefore, synthetic retinoids were developed, such as the atypical adamantyl retinoid ST1926 that provides enhanced bioavailability and reduced toxicity. We have assessed the in vitro and in vivo antitumor properties and mechanism of action of ST1926 in targeting cancer stem-like cells population of human prostate cancer (PCa) cell lines, DU145 and PC3, and mouse PCa cell lines, PLum-AD and PLum-AI. We demonstrated that ST1926 substantially reduced proliferation of PCa cells and induced cell cycle arrest, p53-independent apoptosis, and early DNA damage. It also decreased migration and invasion of PCa cells and significantly reduced prostate spheres formation ability in vitro denoting sufficient eradication of the self-renewal ability of the highly androgen-resistant cancer stem cells. Importantly, ST1926 potently inhibited PCa tumor growth and progression in vivo. Our results highlight the potential of ST1926 in PCa therapy and warrant its clinical development.

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