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Adapalene Inhibits Prostate Cancer Cell Proliferation In Vitro and In Vivo by Inducing DNA Damage, S-phase Cell Cycle
Hai-Bin Nong1, Ya-Nan Zhang2, Yi-Guang Bai1,3
1Department of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, China.
Abstract:
Aims: Prostate cancer is a well-known aggressive malignant tumor in men with a high metastasis rate and poor prognosis. Adapalene (ADA) is a third-generation synthetic retinoid with anticancer properties. We investigated the anti-tumor activity and molecular mechanisms of ADA in the RM-1 prostate cancer cell line in vivo and in vitro. Methods: The effects of ADA on cell proliferation were estimated using the CCK-8 and colony formation assays. The wound-healing assay and the Transwell assay were employed to examine the migratory capacity and invasiveness of the cells. Flow cytometry was utilized to evaluate the cell cycle and apoptosis, and Western blotting analysis was used to assess the expression of the associated proteins. Micro-CT, histomorphological, and immunohistochemical staining were used to assess the effects of ADA on bone tissue structure and tumor growth in a mouse model of prostate cancer bone metastasis. Result: ADA dramatically inhibited cell proliferation, migration, invasiveness, and induced S-phase arrest and apoptosis. ADA also regulated the expression of S-phase associated proteins and elevated the levels of DNA damage markers, p53, and p21 after ADA treatment, suggesting that the anti-tumor effect of ADA manifests through the DNA damage/p53 pathway. Furthermore, we observed that ADA could effectively inhibited tumor growth and bone destruction in mice. Conclusion: ADA inhibited prostate cancer cell proliferation, elicited apoptosis, and arrested the cell cycle in the S-phase. ADA also slowed the rate of tumor growth and bone destruction in vitro. Overall, our results suggest that ADA may be a potential treatment against prostate cancer.
Insights
Adapalene (ADA) significantly inhibits prostate cancer cell growth, migration, and invasion by inducing DNA damage and apoptosis. This synthetic retinoid shows potential as a novel treatment for prostate cancer, reducing tumor growth and bone destruction.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Prostate cancer is an aggressive malignancy with high metastasis and poor prognosis.
- Adapalene (ADA), a synthetic retinoid, possesses known anticancer properties.
- Investigating ADA's anti-tumor effects and mechanisms in prostate cancer is crucial.
Purpose of the Study:
- To evaluate the anti-tumor activity of Adapalene (ADA) in prostate cancer.
- To elucidate the molecular mechanisms underlying ADA's anti-cancer effects.
- To assess ADA's efficacy in a mouse model of prostate cancer bone metastasis.
Main Methods:
- Cell proliferation, migration, and invasion assays (CCK-8, colony formation, wound-healing, Transwell).
- Flow cytometry for cell cycle and apoptosis analysis; Western blotting for protein expression.
- In vivo studies using a mouse model with micro-CT and histological analysis.
Main Results:
- ADA significantly inhibited prostate cancer cell proliferation, migration, and invasion.
- ADA induced S-phase cell cycle arrest and apoptosis, linked to the DNA damage/p53 pathway.
- ADA effectively suppressed tumor growth and bone destruction in vivo.
Conclusions:
- Adapalene demonstrates potent anti-prostate cancer activity by inhibiting proliferation and inducing apoptosis.
- ADA treatment leads to S-phase arrest and impacts key molecular pathways involved in DNA damage.
- Adapalene shows promise as a therapeutic agent for prostate cancer, including its metastatic bone lesions.
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