Antiproliferative and pro-apoptotic effects of quercetin on human pancreatic carcinoma cell lines EPP85-181P and EPP85-181RDB.

Abstract

Polyphenols are present in several edible plants and for many years induce high interest mainly due to their antioxidative and anti-inflammatory influence. At present, numerous studies are conducted on antineoplastic effects of the compounds. One of most effective biopolyphenols involves the flavonol quercetin. Our studies aimed at evaluation of antiproliferative and pro-apoptotic effects of quercetin alone and in combinations with daunorubicin on cells of human pancreatic carcinoma lines. The experiments were conducted on two cell lines, sensitive to daunorubicin EPP85-181P line, and its resistant variant EPP85-181RDB. Effect of studied substances on cell proliferation was detected using sulphorhodamine B (SRB) protein staining method. Apoptotic damage was estimated using comet and TUNEL techniques. Our data demonstrated that quercetin exerted cytotoxic action on cells of the both neoplastic cell lines in concentration-dependent manner. In the case of EPP85-181RDB cell line, quercetin seemed to sensitize resistant cells to daunorubicin. In parallel, the effect of both substances on the sensitive cell line was synergistic. Results of the studies confirmed that quercetin may probably break resistance of neoplastic cells to chemotherapy. On the other side, studied flavonol augmented action of cytostatic drug in case of sensitive tumour cells what suggest, that it might allow to decrease dosage of cytostatic drugs and reduce negative side effects of the treatment.

Dietary Polyphenols in Cancer Chemoprevention: Implications in Pancreatic Cancer

“…The authors have also explored the cellular model systems to test the sensitivity or resistance to agents, to further define the translational significance of quercetin to be used in combination treatment approaches for pancreatic cancer. In one such study, Borska et al determined the effects of quercetin on the daunorubicin sensitive EPP85-181P cell line, as well as the daunorubicin resistant EPP85-181RDB cell line [56]. An active area of research in preclinical models is to determine whether the bioavailability of orally or intraperitoneally administered quercetin results in sufficient systemic concentrations that could result in a sustained anti-tumoral activity.…”

“…Quercetin exposure was found to reduce cell proliferation and increase apoptosis in both the cell lines in a dose-dependent manner. Importantly, quercetin combined with daunorubicin induced synergistic effects in daunorubicin-sensitive cells, and also, sensitized the daunorubicin-resistant cells to daunorubicin cytotoxic effects [56]. Another report by the same group later identified the role of P-glycoprotein (ABCB1), one of the ABC transporters reported to induce chemoresistance via its ability to expel drugs outside of cells [57].…”

The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms

“…The application of quercetin to inhibit tyrosine kinase has been approved for clinical trials [ 135 ]. The anti-cancer potential of quercetin has been shown in various in vitro and in vivo studies [ 136 , 137 , 138 , 139 ]. Down-regulation of mTOR activity, and the subsequent formation of autophagosomes by quercetin treatment, have been evidenced [ 140 ].…”

Investigation of bioactive compounds with anti-cancer potential in Carica papaya leaves

“…In vitro studies on:  human lung cancer cell line (Zheng et al, 2012)  human prostate adenocarcinoma cell line (Noori-Daloii et al, 2011, Maurya et al, 2011)  human monocytic cell line U937 (Kim et al, 2011b)  human glioblastoma cell line T98G (Nakatsuma et al, 2010)  human pancreatic carcinoma cell (Borska et al, 2010).…”