Abstract

CYTOTOXIC POTENTIAL AND MECHANISM OF ACTION OF HETERONEMIN IN PROSTATE CANCER: A COMPREHENSIVE REVIEW

Agilandeswari Devarajan, Yash Srivastav, Prateek Mangal, Anil Kumar, Konda V.V. S. Krishna, Sanmati Kumar Jain, Manoj Kumar Katual, Bhiresh Kumar and Uriti Sri Venkatesh*

Abstract

Background: Prostate cancer remains a significant health challenge, with existing treatment modalities often limited by resistance and adverse effects. Natural compounds continue to offer promising alternatives in oncology. Heteronemin, a steroidal saponin isolated from marine sponges, has emerged as a potential therapeutic agent due to its notable cytotoxic effects and relatively favorable safety profile in preclinical studies. Objective: This review aims to provide a comprehensive evaluation of heteronemin’s cytotoxic potential and elucidate its mechanisms of action in the context of prostate cancer. Additionally, it explores the safety profile and clinical implications of heteronemin, highlighting its potential as a novel therapeutic option. Methods: The review synthesizes data from recent studies on heteronemin's cytotoxicity, focusing on its impact on prostate cancer cell lines and animal models. Mechanistic insights into its action, including apoptosis induction, cell cycle arrest, and modulation of key signaling pathways, are discussed. Safety and toxicity profiles are examined based on preclinical findings. Results: Heteronemin demonstrates significant cytotoxicity against prostate cancer cells, inducing apoptosis via intrinsic and extrinsic pathways and arresting the cell cycle predominantly in the G1 phase. It effectively inhibits critical signaling pathways such as PI3K/Akt and MAPK, which are essential for cancer cell survival and proliferation. Safety assessments reveal minimal acute and chronic toxicity, with no significant adverse effects on major organs, hematological parameters, or reproductive health in animal models. Conclusion: Heteronemin shows promise as a novel therapeutic agent for prostate cancer, with its potent cytotoxic effects and manageable safety profile supporting further clinical investigation. Future research should focus on optimizing pharmacokinetics, exploring combination therapies, and conducting clinical trials to establish its efficacy and safety in human patients. The potential for heteronemin to integrate into existing treatment regimens and address current therapeutic challenges underscores its significance in advancing prostate cancer therapy.

Keywords: Heteronemin, Prostate Cancer, Cytotoxicity, Mechanism of Action, Safety Profile, Clinical Implications, Natural Compounds.