Hyptolide Promotes Breast Cancer Stem Cells Apoptosis and S-phase Cell Cycle Arrest

Articles in Press

Document Type : Research Articles

Authors

1 Chemistry Department, Faculty of Sciences and Mathematics, Universitas Diponegoro, Semarang, Indonesia.

2 Pharmaceutical Sciences Department, Faculty of Medicine, Universitas Negeri Semarang, Semarang, Indonesia.

Abstract

Objective: Breast cancer stem cells (BCSCs) develop apoptosis resistance by expressing pro and antiapoptotic proteins. The induction of apoptosis is an important mechanism of action for many anticancer agents. However, recently chemotherapy-induced chemoresistance and increased relapse phenomenon due to BCSCs population-targeted therapy failure. Therefore, treatment using a new compound was supposed to inhibit apoptosis resistance and increase the possibility of cancer apoptosis in the BCSCs population. This study aimed to investigate the effects of the hyptolide, isolate a compound from Hyptis pectinata on apoptosis induction in BCSCs. Methods: The cytotoxic activity was analyzed using MTT assay. Annexin V-Propidium Iodide measured apoptosis under flow cytometry. Cell cycle arrest was assessed by flow cytometry. The molecular target, key protein, and molecular mechanism of hyptolide targeting BCSCs were determined by bioinformatic analysis. Result: Hyptolide inhibited BCSCs cell growth with an IC50 value of 55 µg/mL. The hyptolide cytotoxic effect by apoptosis induction up to 32% through S-phase cell cycle arrest in a dose-dependent manner through regulation of SRC, EGFR, and MAPK1 signaling pathway. Conclusion: Taken together, hyptolide has potential for treating BCSCs by targeting SRC, EGFR, and MAPK1 signaling. Further investigation of the molecular mechanisms involved is required to develop hyptolide as a BCSC-targeted drug.

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Main Subjects

Asian Pacific Journal of Cancer Prevention

Articles in Press, Accepted Manuscript
Available Online from 13 September 2025

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History

  • Receive Date: 03 March 2022
  • Revise Date: 07 May 2023
  • Accept Date: 31 August 2025

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