KEY TAKEAWAYS
- The study aimed to investigate EPHA2’s role in cisplatin resistance and assess sesamol’s potential to enhance sensitivity in cervical cancer.
- Researchers noticed that targeting EPHA2 with sesamol effectively enhances cisplatin sensitivity in cervical cancer by modulating key cellular pathways.
Cervical cancer, the 4 most common cancer among women globally, presents substantial treatment challenges due to its resistance to cisplatin. Ephrin type-A receptor 2 (EPHA2) is significantly overexpressed in cervical cancer and is a key factor in cisplatin resistance, though its mechanisms are not fully clarified.
Critical processes such as mitochondrial dynamics, autophagy, and mitophagy contribute to this resistance. Sesamol, a promising phytochemical with anticancer potential, might offer a solution.
P P Mubthasima and the team aimed to explore how EPHA2 regulates these processes and examine sesamol’s ability to overcome cisplatin resistance and impede cervical cancer progression.
In this study, EPHA2 was knocked down in the SiHa cell line to evaluate changes in molecular markers related to mitochondrial dynamics, mitophagy, and autophagy. The results showed that EPHA2 knockdown (EPHA2-KD) led to increased mitochondrial fusion and decreased mitochondrial fission, mitophagy, and autophagy.
Additionally, the effects of EPHA2-KD and sesamol treatment on cisplatin sensitivity were investigated. Data indicated that EPHA2-KD and sesamol treatment significantly enhanced cellular sensitivity to cisplatin-induced cytotoxicity. Moreover, sesamol effectively targeted EPHA2, as evidenced by reduced EPHA2 expression levels following sesamol treatment.
The study concluded that targeting EPHA2 through knockdown or sesamol treatment enhances cisplatin sensitivity in cervical cancer by modulating mitochondrial dynamics, autophagy, and mitophagy, suggesting promising therapeutic strategies to overcome chemoresistance.
The study was funded by DST -Science and Engineering Research Board (DST-SERB) – ECR/2018/000894.
Source: https://pubmed.ncbi.nlm.nih.gov/39222165/
Mubthasima PP, Singh SA, Kannan A. (2024). “Sesamol-mediated targeting of EPHA2 sensitises cervical cancer for cisplatin treatment by regulating mitochondrial dynamics, autophagy, and mitophagy.” Mol Biol Rep. 2024;51(1):949. Published 2024 Sep 2. doi:10.1007/s11033-024-09875-x
