Abstract
About this talk
Introduction
Natural polyphenols and omega-3 fatty acids have been widely studied for their cancer-inhibiting properties, many of which are mediated by effects on cellular metabolism and mitochondrial function. This paper reviews evidence for alpha-lipoic acid, apigenin, berberine, curcumin, and selected others, focusing on their proven effects against specific cancer types and their actions on mitochondria.
Breast Cancer
Alpha-lipoic acid (ALA) improves mitochondrial bioenergetics, reduces oxidative stress, and can restore apoptosis sensitivity in breast cancer cells by enhancing mitochondrial membrane potential and triggering cytochrome c release (Tripathi et al.). Apigenin causes mitochondrial dysfunction and promotes apoptosis through reactive oxygen species (ROS) generation and mitochondrial membrane depolarization. Berberine targets mitochondria by disrupting membrane potential, increasing ROS, and activating mitochondrial apoptosis pathways (Zhu et al.). Curcumin induces mitochondrial permeability transition and cytochrome c release, leading to apoptosis (Zoi et al.). Other compounds such as quercetin and fisetin also destabilize mitochondrial membranes, promoting cancer cell death.
Lung Cancer
ALA inhibits lung cancer cell proliferation by targeting mitochondrial bioenergetics and reducing stemness, often by downregulating mitochondrial enzymes and increasing mitochondrial-mediated apoptosis (Phiboonchaiyanan and Chanvorachote; Yang et al.). Berberine disrupts mitochondrial function by depolarizing the mitochondrial membrane and promoting apoptosis through the intrinsic pathway (Zhu et al.). Curcumin causes mitochondrial dysfunction, triggers ROS production, and induces apoptosis via mitochondrial cytochrome c release. Quercetin targets mitochondrial integrity, amplifying apoptosis in lung cancer cells.
Liver Cancer
ALA decreases hepatocellular carcinoma progression by modulating mitochondrial antioxidant enzymes and promoting p53-mediated mitochondrial apoptosis (Addissouky). Berberine activates mitochondrial apoptosis by increasing mitochondrial ROS and depolarizing the mitochondrial membrane (Zhu et al.). Curcumin inhibits tumor growth by reducing mitochondrial membrane potential, generating ROS, and activating intrinsic apoptosis (Zoi et al.). Resveratrol and rutin also impair mitochondrial function and enhance apoptosis in liver cancer models.
Colorectal and Gastric Cancer
Berberine induces apoptosis in colorectal and gastric cancer via mitochondrial membrane depolarization, increased ROS, and caspase activation (Sun et al.). Curcumin’s effects include mitochondrial membrane permeabilization and ROS-mediated mitochondrial dysfunction, leading to apoptosis (Mansouri et al.). EGCG and quercetin both promote mitochondrial ROS and depolarization, resulting in cancer cell death.
Prostate Cancer
Curcumin inhibits androgen signaling and triggers mitochondrial apoptosis in prostate cancer cells. Apigenin impairs mitochondrial function and induces cytochrome c release, promoting apoptosis. EGCG and quercetin destabilize mitochondrial membranes and increase ROS, enhancing cytotoxicity.
Pancreatic Cancer
Curcumin and berberine both induce mitochondrial dysfunction in pancreatic cancer, leading to apoptosis via cytochrome c release and ROS generation. Quercetin and resveratrol further compromise mitochondrial integrity, amplifying cell death.
Head and Neck Cancers
Apigenin increases apoptosis and mitochondrial dysfunction in head and neck squamous cell carcinoma, with evidence of mitochondrial membrane depolarization (Chan et al.). Curcumin and quercetin similarly disrupt mitochondrial function, triggering cancer cell death.
Oral Cancer
Apigenin suppresses proliferation and triggers mitochondrial apoptosis in oral squamous cell carcinoma (Pei et al.). Curcumin and quercetin induce mitochondrial depolarization and cytochrome c release in oral cancer models.
Skin Cancer (Melanoma)
Apigenin, curcumin, and resveratrol all potentiate mitochondrial dysfunction in melanoma. Apigenin induces ROS accumulation and ATP depletion via mitochondrial impairment (Jangdey et al.; Lee et al.). Curcumin and resveratrol depolarize mitochondrial membranes and induce apoptosis.
Lymphoma and Leukemia
Curcumin, quercetin, rutin, and resveratrol each promote mitochondrial-mediated apoptosis in lymphoma and leukemia by increasing ROS and activating the intrinsic death pathway (Shanmugam et al.).
Brain Tumors (Glioblastoma)
Curcumin, resveratrol, and apigenin disrupt mitochondrial function in glioblastoma, leading to apoptosis through loss of mitochondrial membrane potential and increased ROS.
Mesothelioma
Apigenin induces necroptosis and mitochondrial dysfunction, with evidence for ATP depletion and ROS accumulation in mesothelioma cells (Lee et al.).
Other Cancer Types
Rosmarinic acid, luteolin, sulforaphane, ursolic acid, and omega-3s broadly induce mitochondrial dysfunction in various cancers by increasing ROS, causing depolarization, and promoting mitochondrial apoptosis. Omega-3 fatty acids, including those in krill oil, elevate mitochondrial ROS, disrupt membrane potential, and sensitize cancer cells to apoptosis in a wide range of tumor types.
Conclusion
Across nearly every major cancer type, polyphenols and omega-3s exert their anti-cancer effects in large part via mitochondria: disrupting energy metabolism, increasing oxidative stress, and activating intrinsic apoptosis. These findings highlight mitochondria as a critical target for natural anticancer therapies, warranting further research and clinical investigation.
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