TARGETING CANCER METABOLISM: THE EFFECTS OF A NOVEL MITOCHONDRIAL PEPTIDE ON CANCER PROGRESSION
Jung-Gi Min, Brandon Glousman, Changhan Lee.
Davis School of Gerontology, University of Southern California, Los Angeles, Los Angeles, CA.
In the early 1920s, Nobel laureate Otto Warburg hypothesized that cancer is a metabolic disease, specifically a mitochondrial dysfunction, based on his observation that cancer cells consume significantly more glucose, an observation now commonly referred to as the Warburg effect. It stands to reason that a potential target for cancer treatment would be related to the mitochondria, the organelle central to a cell’s proliferation through their generation of cellular energy as well as biosynthetic precursors that serve as building blocks for a dividing cell. However, the precise metabolic regulatory mechanisms of this essential organelle are not fully understood. Most of current biology has focused on how the cell communicates to the mitochondria to modulate cellular metabolism, but relatively little is known about how mitochondria influence the cell. The recent discovery of mitochondria-derived peptides (MDP) positions mitochondria as a proactive and influential organelle that regulates cellular metabolism. In this study, we examined the effects of a particular MDP called MOTS-c on the progression of various cancer models through proliferation assays both in vitro and in vivo. Our results in various cancer cell lines (22Rv1, PC3, LnCAP) as well as animal models (BALB/c, NOD SCID) show a profound anti-proliferative effect with MOTS-c treatment, an effect which appears to stem from the mitochondrial peptide’s manipulation of powerful metabolic pathways. This study portrays the possibility of retarding the proliferation of cancer by targeting cellular metabolism, as well as the potential role of the mitochondria as a significant communicator in the progression of cancer.