Somi Kim Cho
Jeju National University, Republic of Korea
Title: Therapeutic implication of the phytochemicals in human gastric cancer cells
Biography
Biography: Somi Kim Cho
Abstract
The cysteine-rich angiogenic inducer 61 (CYR61), an extracellular matrix-associated protein, is involved in survival, tumorigenesis, and drug resistance. There is an increasing demand for developing agents that target CYR61. Hence, we study the effects of flavones against CYR61-overexpressing human gastric adenocarcinoma AGS (AGS-cyr61) cells. Quercetin (1) down-regulates CYR61 and concomitantly decreases in the levels of MRP1 (multidrug resistance-associated protein 1) and nuclear factor NF-kappa B (κB) p65 subunit, (2) reverses multidrug resistance, and (3) inhibits colony formation in AGS-cyr61 cells. AGS-cyr61 cells treated with quercetin at sub IC50 over a range of 5-FU or ADR concentrations manifested strong synergistic effects with these two drugs. Our results demonstrate that CYR61 is a potential regulator of ABC transporters and quercetin can be the novel agent that improves the efficacy of anticancer drugs by down-regulating CYR61 and ABC transporters.
Histone deacetylase 6 (HDAC6) is a unique cytoplasmic enzyme which contributes to malignant progression in various cancer. We found that compound D inhibits HDAC6 activity, increases acetylated α-tubulin, reduces the level of β-catenin, and suppresses cell proliferation. Increase of α-tubulin acetylation by compound D resulted in tubulin polymerization, and consequently, induced aberrant mitosis. Moreover, treatment with high concentrations of compound D induces cell death by mitotic catastrophe, whereas low concentration of compound D induces senescence with upregulation of p21 and Rb, and increase in the phosphorylation of mTOR and the β-galactosidase activity. Therefore, compound D can also be considered as a promising new candidate for anti-cancer drug development.