Quercetin Suppresses Proliferation of Liver Cancer Cell Lines In Vitro

Abstract

Background/Aim: We investigated the antiproliferative effect of quercetin on liver cancer cell lines. Materials and Methods: Thirteen liver cancer cell lines were cultured followed by treatment with varying concentrations of quercetin (0-100 μM) or quercetin and 5-FU, and the cell viability was analysed by the MTT assay. Flow cytometry was also used to examine cell cycle progression after treatment with quercetin. Results: The addition of quercetin resulted in a dose-and time-dependent suppression of cell proliferation. In some cell lines, treatment with quercetin and 5-FU caused an additional or synergistic effect. Most cell lines displayed cell cycle arrest at different phases of the cell cycle. Conclusion: Quercetin inhibits the proliferation of liver cancer cells via induction of apoptosis and cell cycle arrest.Hepatocellular carcinoma (HCC) is the most frequent primary cancer, and an important medical problem (1). Many HCC patients have a history of chronic hepatitis or liver cirrhosis caused by Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection (2-4). Treatments for poor liver function associated with hepatitis are limited and outcomes are poor. Even with the most successful treatments, the 5year recurrence rate of HCC is very high (1). Treating and preventing recurrence is critical for improving survival rates.Quercetin is a type of flavonoid contained in many plants, and possesses antioxidant, anti-inflammatory, and immuno-logical capabilities (5). Quercetin can suppress cell proliferation and induce apoptosis in human cancers, including breast, lung, oral, and prostate; however, there is no report on its effect on liver cancer (6-9). In the current study, we examined the antitumor effects of quercetin on 13 HCC cell lines in vitro. Materials and MethodsCell lines and cell culture. This study utilized 11 HCC cell lines (KIM-1, KYN-1, KYN-2, KYN-3, HAK-1A, HAK-1B, HAK-2, HAK-3, HAK-4, HAK-5, and HAK-6), and 2 human combined hepatocellular and cholangiocarcinoma (CHC) cell lines (KMCH-1 and KMCH-2). The cell lines were originally established in the Department of Pathology, Kurume University Faculty of Medicine, and each of them retains the morphological and functional features of the original tumor as previously described (10-18). Each cell line was grown in Dulbecco's modified Eagle medium (Nissui Seiyaku, Co., Japan) supplemented with 2.5% heat-inactivated (56˚C, 30 min) fetal bovine serum (Bioserum, Victoria, Australia), 100 U/ml penicillin, 100 μg/ml streptomycin (GIBCO BRL/Life Technologies, Inc., Gaithersburg, MD, USA) and 12 mmol/l sodium bicarbonate, in a 5% CO 2 humidified atmosphere at 37˚C. Effects of quercetin on the proliferation of hepatocellular carcinoma and combined hepatocellular and cholangiocarcinoma cell lines in vitro.The effects of quercetin with and without 5-FU on proliferation were examined using 3-(4,5-dimethylthiazol-2yl-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay kit (Chemicon, Temecula, CA, USA) as previously described (10). Quercetin was obtained from Sigma Chem...

Potential Therapeutic Targets of Quercetin, a Plant Flavonol, and Its Role in the Therapy of Various Types of Cancer through the Modulation of Various Cell Signaling Pathways

“…Hepatocellular carcinoma Qu prevents the liver cancerous cells proliferation through initiation of apoptosis and cell cycle arrest. [151] Colon cancer Induction of apoptosis was noticed in colon cancer through the Qu treatment. [152] Renal cancer Qu mitigates the adverse impact of sunitinib (a primary renal cancer treating drug); Qu-3-O-β-D-glucopyranoside was observed-that is, iso-Qu has an enhanced pharmacokinetic report.…”

“…Another in vitro study, conducted by Hisaka et al, stated that Qu prevents the liver cancerous cell proliferation through initiation of apoptosis and cell cycle arrest. Liver cell lines were treated with different dosages of varying concentrations of Qu, and cell viability along with cell cycle progression, were assessed, which concluded that treatment with Qu and 5-Fuorouracil caused a synergetic effect, and most cell lines showed cell cycle arrest at different cell cycle stages [151]. Qu regulates other related signaling pathways via initiation of the phosphorylation of Sp-1, Src-1, and STAT5, which are responsible for the progression of cancer [228].…”

An insight into anticancer, antioxidant, antimicrobial, antidiabetic and anti-inflammatory effects of quercetin: a review

“…Quercetin showed remarkable inhibitory effects on malignant cells like breast, lung, gastric, ovarian, colorectal and hepatic cancers [ 11 ]. Anticancer effects of quercetin were reported due to several mechanisms like cell apoptosis, inhibition of angiogenesis, inhibiting P-gp channel, decreasing oncogene expression and regulating specific signaling pathways [ 12 ].…”

The molecular basis of the anticancer properties of quercetin

“…In this regard, it has been demonstrated that quercetin suppressed hepatocellular carcinoma (HCC) cell proliferation in a concentration-and timedependent manner as well as induced cell-cycle arrest at different phases, in relation to the cell line employed. Among the 13 HCC cell lines tested, quercetin blocked cell cycle in G0/G1, S or G2/M phases in 4, 2 and 6 lines, respectively [10]. In HepG2 cell lines, quercetin reduced cell proliferation along with lowering the expression of the checkpoint kinase-1 (CHEK1), leading to the downstream regulation of both cyclins A and E and hence the cell-cycle blockage [11].…”