HomeIngredientColon Cancer Cell Death by Synergistic Activity of Phytochemicals is Modulated by Increased ROS, Activation of AMPK, and Inhibition of mTORC1

Colon Cancer Cell Death by Synergistic Activity of Phytochemicals is Modulated by Increased ROS, Activation of AMPK, and Inhibition of mTORC1

August 20, 2022

FASEB J. 2022 May;36 Suppl 1. doi: 10.1096/fasebj.2022.36.S1.0R812.

ABSTRACT

Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States, and has high prevalence in both men and women. Consumption of foods high in fruits, vegetables, and spices is strongly associated with a reduced risk of developing cancer, and may be attributable to the synergy of phytochemicals present in the diet. Previously, we have shown that combinatorial treatment with curcumin and silibinin B (CS) led synergistically to higher rates of colon cancer cell death in comparis on to single compound treated cells. Our goal is to elucidate the molecular and signaling mechanisms of the synergistically enhanced anticancer activity mediated by CS in CRC. Cancer cells maintain high energy levels by higher rates of glycolysis and lactic acid fermentation, occurring in the abundance of oxygen, and have elevated levels of reactive oxygen species (ROS) compared to normal cells. Cancer cells adapt to increased levels of ROS by developing ROS scavenging mechanisms. Despite this, the ROS levels are higher than in normal cells. Phytochemicals have been shown to increase ROS by interfering with enzymes involved in reducing ROS. Our hypothesis is that phytochemical-based disruption of ROS scavenging mechanisms increases ROS to higher levels, which leads to the activation of AMPK. Activated AMPK, in turn, inhibits the mTOR pathway thereby increasing cell death by apoptosis and autophagy. Our initial results showed increased ROS and activated AMPK in combinatorial treated cells compared to single compound and control treated cells.

PMID:35555828 | DOI:10.1096/fasebj.2022.36.S1.0R812

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About The Author

Patrick Blanchard MD

Meet Dr. Blanchard Dr. Blanchard’s medical practice is an embodiment of Integrative health which brings conventional and complementary approaches together in a coordinated way. Conveniently located in sunny Florida and over the internet with ValiseMD’s secure HIPPA compliant telXmed servers. Since 1994, patients with a wide range of challenging medical problems have achieved optimum health using the best of natural medicine, judiciously combined with high-tech innovations. Breakthroughs are often achieved even after patients have consulted mainstream specialists and holistic practitioners. Dr. Blanchard is founder and CEO of ValiseMD, Inc. He is board certified in Family Medicine since 1994 and awarded Fellow of the American Academy of Family Physicians in 2001. He received the ‘Teacher of the Year’ award from the University of Kansas School of Medicine at completion of his residency in Family Medicine. He completed a fellowship at Wake Forest University in the field of vascular neurosonology. He holds a medical patent in the field of Gastroenterology. He holds an unrestricted license to practice medicine and surgery in Florida. He started his medical career as a Emergency Medical Technician, then as a Paramedic and later a Medical Doctor.