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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)1208-1220
Number of pages13
JournalMolecular Carcinogenesis
Volume58
Issue number7
DOIs
Publication statusPublished - Jul 2019

Fingerprint

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

Cite this

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.

In: Molecular Carcinogenesis, Vol. 58, No. 7, 07.2019, p. 1208-1220.

Research output: Contribution to journalArticle

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, vol. 58, no. 7, pp. 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. In: Molecular Carcinogenesis. 2019 ; Vol. 58, No. 7. pp. 1208-1220.
@article{0705f7e40a554f8aa812fdf558bb55bd,
title = "The synthetic retinoid ST1926 attenuates prostate cancer growth and potentially targets prostate cancer stem-like cells",
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.",
author = "Bahmad, {Hisham F} and Houda Samman and Alissar Monzer and Ola Hadadeh and Katia Cheaito and Rana Abdel-Samad and Berthe Hayar and Claudio Pisano and Hiba Msheik and Yen-Nien Liu and Nadine Darwiche and Wassim Abou-Kheir",
note = "{\circledC} 2019 Wiley Periodicals, Inc.",
year = "2019",
month = "7",
doi = "10.1002/mc.23004",
language = "English",
volume = "58",
pages = "1208--1220",
journal = "Molecular Carcinogenesis",
issn = "0899-1987",
publisher = "Wiley-Liss Inc.",
number = "7",

}

TY - JOUR

T1 - The synthetic retinoid ST1926 attenuates prostate cancer growth and potentially targets prostate cancer stem-like cells

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.

PY - 2019/7

Y1 - 2019/7

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.

U2 - 10.1002/mc.23004

DO - 10.1002/mc.23004

M3 - Article

C2 - 30883933

VL - 58

SP - 1208

EP - 1220

JO - Molecular Carcinogenesis

JF - Molecular Carcinogenesis

SN - 0899-1987

IS - 7

ER -