Quercetin, one kind of phytochemical, is known to an important anti-cancer flavonoid. In this study, we suggest that quercetin-treated HT-29 colon cancer cells inhibited cell proliferation and induced apoptosis through AMPK, mTOR, VASP and COX-2 signaling pathway. AMP-activated protein kinase (AMPK) acts as an intracellular energy sensor and activated by depletion status of ATP. AMPK has been recognized as an important up-regulation signaling mediator involved in the down-regulation of the mTOR and VASP pathway. Mammalian target of rapamycin (mTOR) plays a central role in regulating of cell proliferation. mTOR signaling pathway is immoderately activated in many type of cancer. We determined with MTT assay, Western blotting and FACS. Treatment of Compound C (AMPK inhibitor) resulted in increased cell proliferation of cancer cells and showed that mTOR, COX-2 and VASP are regulated by AMPK. But, COX-2, VASP are directly controlled by quercetin in AMPK-independent pathway. Also, treatment of rapamycin (mTOR inhibitor), celecoxib (COX-2 inhibitor) and co-treatment with quercetin resulted in greater decrease of cell proliferation in colon cancer cells. In addition, mTOR can modulate the expression of COX-2, and rapamycin functions as an activator of AMPK. The results indicate that quercetin decreases cell proliferation and induces apoptosis by inhibiting mTOR and COX-2. The inhibition of mTOR (or rapamycin) can control the expression of VASP, AMPK. (Cancer Prev Res 16, 340-347, 2011)

Keywords: AMPK, mTOR, VASP, Quercetin, Apoptosis, HT-29 colon cancer cells