Autophagy is a process of self-degradation of cellular components to eliminate unwanted proteins and damaged organelles.  It is a lysosome-dependent degradative pathway frequently activated in tumor cells treated with chemotherapy or radiation in which double-membrane autophagosomes sequester organelles or portions of cytosol and fuse with lysosomes or vacuoles for breakdown by resident hydrolases. Colorectal cancer is a second most leading cause of death from cancer in the world. Natural products and their derivatives have historically been invaluable as a source of therapeutic agents in drug research for cancer treatment. Thymol (5-methyl-2-(1-methylethyl) phenol) is an isomer of carvacrol, having the hydroxyl group at a different location on the phenolic ring. The hydrophobic nature of thymol enables it to react with the lipids of the cell membrane and mitochondria, rendering them permeable and leading to leakage of the cell components. Treatment of colorectal cancer cell HCT 116, with 50, 75, and 100 �M concentrations of thymol decreased cell viability significantly within 16 h with decreased autophagy. To provide evidences we have performed comet assay, chromatin staining, loss of mitochondrial membrane potential (MMP), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and western blotting. Comet assay results prove that induction of apoptosis by thymol does not depends on DNA damage rather dependent on other death related signals, including loss of MMP, formation of pycnonucleus, TUNEL positive, elevated expression of Bax, Caspase, Cyto c, and decreased expression of Bcl-2 , mTOR, and p-Akt.

Thymol induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR inhibition

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.