Oncopreventive and Oncotherapeutic Potential of Plant Secondary Metabolites Against Gastric Cancer: A Review

Gastric cancer, the fifth most prevalent cancer globally, presents a significant challenge for effective treatment. Despite advancements, chemotherapy is often hindered by severe side effects and drug resistance, whereas targeted immunotherapy exhibits inconsistent efficacy. Amidst these challenges, plant secondary metabolites or phytochemicals have emerged as promising agents for the prevention and treatment of gastric cancer. The aim of this review is to perform a comprehensive evaluation of the gastric cancer preventive and therapeutic effects of various phytochemicals with an understanding of related mechanisms of action. A structured literature search was followed to collect preclinical and clinical data on the effects of phytochemicals in combating gastric cancer. Results have indicated that alkaloids, glycosides, polyphenols, sulfur-containing compounds, and terpenoids inhibited gastric cancer cell proliferation in vitro and suppressed gastric tumor growth in vivo. These effects are driven by mechanisms such as alterations of pro-apoptotic and anti-apoptotic proteins, induction of cell cycle arrest, and promotion of apoptosis and autophagy. Additionally, alkaloids and terpenoids influence cancer progression through epigenetic modifications, such as alterations in DNA methylation and histone modifications, as well as through regulating inflammatory pathways, such as the nuclear factor-κB pathway. Moreover, glycosides, polyphenols, and sulfur-containing compounds modulate critical signaling pathways related to cancer cell survival, proliferation, progression, and metastasis, including rat sarcoma/mitogen-activated protein kinase, wingless-related integration site/β-catenin, and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signal transduction pathway. Despite promising preclinical results, further detailed studies, including clinical trials, are crucial to validate the clinical utility of phytochemicals in gastric cancer prevention and therapy.