Lung cancer is the leading cause of
cancer death in many developed countries, including Taiwan.
Quercetin, a widely distributed
bioflavonoid, is well known to induce growth inhibition in a variety of human
cancer cells.
Quercetin glucuronides are the main circulating metabolites after dietary supplements with
quercetin in humans. However, there is little information available as to how
quercetin glucuronides affect human
cancer cells. We investigated the effects of
quercetin glucuronides in a human
lung cancer cell line NCI-H209. We checked the cell viability, cell cycle checkpoint
proteins, pro- and antiapoptotic
proteins,
caspase-3 activity, and gene expression by flow cytometry and Western blot. The viability of cells decreased in a dose- and time-dependent manner. Cell cycle analysis revealed a significant increase of the proportion of cells in G2/M phase and subG0/G1 phase (corresponding to apoptotic cells). Moreover,
quercetin glucuronides increased the expressions of
cyclin B, Cdc25c-ser-216-p, and Wee1
proteins, indicating the G2/M arrest. We also demonstrated a concurrent decrease of the mitochondrial membrane potential, release of
cytochrome c, up-regulation of Bax, down-regulation of Bcl-2, and activation of
caspase-3, and subsequently, cleavage of
poly(ADP-ribose) polymerase. In addition,
quercetin glucuronide-induced apoptosis was totally blocked by the broad-spectrum
caspase inhibitor
benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone. Taken together, we demonstrated that
quercetin glucuronides inhibited proliferation through G2/M arrest of the cell cycle and induced apoptosis via
caspase-3 cascade in the human
lung cancer cell line NCI-H209. Delineation of the biological effects of specific major
quercetin metabolites on chemotherapeutic potential or
chemoprevention of human
cancers warrants further investigation.