Your browser doesn't support javascript.
loading
Lupeol, an androgen receptor inhibitor, enhances the chemosensitivity of prostate cancer stem cells to antiandrogen enzalutamide-based therapy.
Khan, Mohammad Afsar; Singh, Deepti; Jameel, Mohd; Maurya, Santosh K; Singh, Swati; Akhtar, Kafil; Siddique, Hifzur R.
Afiliación
  • Khan MA; Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, India.
  • Singh D; Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, India.
  • Jameel M; Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, India.
  • Maurya SK; Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, India.
  • Singh S; Department of Zoology, University of Delhi, Delhi 110007, India.
  • Akhtar K; Department of Pathology, JNMC, Aligarh 202002, India.
  • Siddique HR; Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, India. Electronic address: hrsiddique@gmail.com.
Toxicol Appl Pharmacol ; 478: 116699, 2023 11 01.
Article en En | MEDLINE | ID: mdl-37777120
Enzalutamide is an androgen receptor (AR) antagonist commonly used in the treatment of prostate cancer (CaP). However, due to the potential toxicity and development of resistance associated with Enzalutamide-based therapy, there is a need to explore additional compounds that can enhance its therapeutic effectiveness while minimizing toxicity. Lupeol is a pharmacologically active triterpene having anticancer effects. The objective of this study was to explore Lupeol's potential in enhancing the chemosensitivity of chemoresistant CaP cells to Enzalutamide in vitro and in a mouse model. To test our hypothesis, we performed cell viability and luciferase reporter gene assay, flow cytometry, animal studies, and histopathological analysis. Finally, we analyzed the change in selective metabolites in the prostate tissue by LCMS. Results demonstrated that a combination of Lupeol and Enzalutamide could better (i) suppress the Cancer Stem Cells (CSCs) and chemoresistant cells (PTEN-CaP8 and PC3) viability and migration, (ii) increase cell cycle arrest, (iii) inhibit the transcriptional activity of AR, c-MYC, c-FLIP, and TCF (iv) inhibit tumor growth in a mouse model (v) protect Enzalutamide-induced adverse effects in prostate glands and gut tissue (vi) decrease levels of testosterone and methionine metabolites. In conclusion, Lupeol enhances the pharmacological efficacy of Enzalutamide and reduces the adverse effects. Thus, Lupeol could be a promising adjuvant for improving Enzalutamide-based treatment outcomes and warrant further research.
Asunto(s)
Palabras clave

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Receptores Androgénicos / Neoplasias de la Próstata Resistentes a la Castración Límite: Animals / Humans / Male Idioma: En Revista: Toxicol Appl Pharmacol Año: 2023 Tipo del documento: Article País de afiliación: India

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Receptores Androgénicos / Neoplasias de la Próstata Resistentes a la Castración Límite: Animals / Humans / Male Idioma: En Revista: Toxicol Appl Pharmacol Año: 2023 Tipo del documento: Article País de afiliación: India