The synthetic retinoid ST1926 attenuates prostate cancer growth and potentially targets prostate cancer stem‐like cells
Autor: | Katia Cheaito, Hisham F. Bahmad, Wassim Abou-Kheir, Berthe Hayar, Nadine Darwiche, Claudio Pisano, Hiba Msheik, Yen-Nien Liu, Alissar Monzer, Houda Samman, Rana Abdel-Samad, Ola Hadadeh |
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Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Cancer Research Carcinogenesis medicine.drug_class Population Adamantane Antineoplastic Agents Apoptosis Biology urologic and male genital diseases Mice Retinoids 03 medical and health sciences Prostate cancer 0302 clinical medicine DU145 Cell Movement Cancer stem cell Cell Line Tumor medicine Animals Humans Neoplasm Invasiveness Retinoid education Molecular Biology Cell Proliferation education.field_of_study Prostate Prostatic Neoplasms Cancer Cell Cycle Checkpoints medicine.disease Xenograft Model Antitumor Assays 030104 developmental biology Cinnamates Cell culture 030220 oncology & carcinogenesis Cancer cell Neoplastic Stem Cells Cancer research DNA Damage |
Zdroj: | Molecular Carcinogenesis. |
ISSN: | 1098-2744 0899-1987 |
Popis: | 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. |
Databáze: | OpenAIRE |
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