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Research Paper|Volume 16, Issue 19|pp 12820—12832

Anticancer potential of isoalantolactone in testicular cancer: an analysis of cytotoxicity, apoptosis, and signaling pathways

Ming-Tse Sung1, Hsuan-En Huang2, Ya-Chuan Chang2,3, Chia-Ying Yu2,3, Hao-Lun Luo4,5, Wen-Wei Sung2,3,6
  • 1Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
  • 2School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
  • 3Department of Urology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
  • 4Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
  • 5Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
  • 6Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
* Equal contribution
Received: March 13, 2024Accepted: July 18, 2024Published: October 9, 2024
https://doi.org/10.18632/aging.206076

Copyright: © 2024 Sung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Testicular cancer, a highly prevalent malignancy among young adults, has witnessed an alarming rise in recent decades. This study delves into the therapeutic potential of isoalantolactone (IATL), a natural product extracted from Inula helenium and Inula racemosa, against testicular cancer. Employing MTT assays and flow cytometry, we observed a dose-dependent reduction in cell viability and induction of cell cycle arrest at sub-G1 phase with increasing IATL concentrations. Furthermore, Annexin V/PI dual staining revealed IATL-induced apoptosis. Human Apoptosis Array analysis demonstrated IATL’s influence on HIF-1α and TNF R1 expression, implicating its role in cancer cell growth and death regulation. Next-generation sequencing (NGS) and pathway analysis highlighted the involvement of ferroptosis and HIF-1 signaling in IATL-mediated effects. Western blotting validated the downregulation of key proteins associated with apoptosis inhibition and activation, confirming IATL’s potential as an anticancer agent. Moreover, IATL induced ferroptosis by modulating expression levels of GPX4, xCT, NRF2, and HO-1. Our findings shed light on IATL’s multifaceted anticancer mechanisms, emphasizing its potential as a therapeutic candidate for testicular cancer.