Natural product-induced apoptosis in oral squamous cell carcinoma via targeting mitochondrial multifunctionality

Background Mitochondria, as the regulatory center of cellular energy metabolism, can influence ATP synthesis, redox balance, and apoptotic pathways. Recent studies have confirmed that some natural products, due to their self-assembling properties and multi-target effects, can inhibit OSCC progression by regulating mitochondrial function, providing key lead compounds for the development of new OSCC therapies. Methods We retrieved data from PubMed, Embase, Web of Science, and CNKI to classify and summarize the relationship between mitochondria and OSCC, as well as the regulatory mechanisms of natural products. Results Natural products exhibit unique advantages in inducing apoptosis in OSCC cells through multi-pathway regulation mechanisms targeting mitochondria. Various active components, such as betaine and Arglabin, induce oxidative stress by promoting ROS accumulation, disrupting mitochondrial redox balance, and thereby activating the intrinsic apoptotic pathway; extracts like cantharidin and berberine induce changes in mitochondrial membrane permeability by regulating the expression ratio of Bcl-2 family proteins, promoting the release of Cyt-c and activating the caspase cascade. It is noteworthy that combining radiotherapy drugs with natural products for OSCC treatment offers greater stability without additive side effects. Moreover, nanodelivery technology, through the design of smart responsive carriers, introduces a competitive release mechanism, achieving precise, on-demand drug release at tumor sites, providing important candidates for the development of new antitumor drugs. Conclusion Natural products targeting mitochondria provide a new direction for the treatment of OSCC, and their potential for clinical translation is expected to overcome existing therapeutic challenges.