Abstract 4664: Co-treatment of cancer cells with DNA damaging drugs and quercetin suppresses cell growth independent of p21 and Bax induction
Authors: Samuel Temesgen , Fadlalla Khalda , Katkoori Venkat , Khazal Kamel , Turner Timothy , Manne Upender 
Published: August 2012

Abstract
Quercetin, one of the most abundant polyphenols, has been evaluated for its potential cancer preventive functions and for its anticancer activity in vitro and in vivo. Its interactions with chemotherapeutics, however, have not been established. Some reports indicate enhancement of drug activity by quercetin but others suggest precautions in co-administering antioxidants such as quercetin and chemotherapeutic drugs. Therefore, further investigations were needed to determine the conditions under which the co-treatment of cancer cells with drugs and quercetin could be clinically beneficial. This study was done to examine how quercetin modulates responses to the chemotherapeutic drugs, 5FU, camptothecin, and VP16, in colon and prostate cancer cells, and to determine the biochemical processes involved in the interactions. Survival of HCT116 colorectal cancer cells (p53 wild-type & null) was determined by assay of clonogenicity of cells exposed to selected concentrations of 5-FU, camptothecin, or VP16 in the presence or absence of quercetin. For cell cycle and biochemical experiments, cells were exposed for 24 hours to 10 µM 5FU, 1 µM camptothecin, or 10 µM VP-16 with or without 50 µM quercetin. The effects of the drugs on the cell cycle were measured by flow cytometry. The induction of p53 and its transcriptional targets, p21 and Bax, as well as the levels of cell cycle regulators, cyclin B1 and survivin, were determined by immunoblotting. Additionally, cell migration assays were used to evaluate the effect of combination treatments on the motility of RKO colorectal and PPC1 prostate cancer cells. Quercetin synergistically inhibited the clonogenicity of the wild-type HCT116 cells, but also inhibited effects on the cell cycle of all the drugs tested. In contrast, for p53-null cells, the combination of low concentrations of 5-FU with up to 6 µM quercetin promoted clonogenic survival. Exposure of wild-type cells to 50 µM quercetin reduced drug-induced up-regulation of p53, p21, and Bax. Combinations of quercetin and the drugs also reduced the levels of cyclin B1 and survivin. RKO and PPC1 cells exposed to the drugs had reduced migratory capacity. Although quercetin alone reduced their migratory capacity, combination treatments did not further reduce cell migration. In summary, quercetin in combination with 5-FU reduced the survival of p53-proficient HCT116 colorectal cancer cells independently of p21 and Bax, but combination of this flavonoid with low concentrations of 5-FU provided a survival advantage for p53-null cells. Further investigations are needed to determine the mechanisms and circumstances under which the combinations of bioactive dietary compounds and chemotherapeutic drugs are beneficial. Supported by grants from NCI/NIH (2U54-CA118948-06, and SC2CA138178).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4664. doi:1538-7445.AM2012-4664