Cytotoxic action of methylquercetins in human lung adenocarcinoma cells

Abstract

Abstract. Lung cancer is the malignant disorder associated with a high number of fatalities in women and men worldwide. Despite continuous improvements in diagnostic strategies and therapeutic modalities over the past decades, the prognosis and survival rate of patients suffering from lung cancer are still unsatisfactory and suggest the requirement for further molecular studies with different lung cancer models. In the present study, the anticancer action of two methylated metabolites of quercetin, isorhamnetin and tamarixetin, was assessed by studying their antiproliferative and apoptosis-inducing potential in human lung adenocarcinoma cell lines, A549 and HCC-44. Both methylquercetins decreased the viability of lung cancer cells at doses significantly lower than those effective for parent quercetin. The IC 50 values measured for isorhamnetin were 26.6 and 15.9 µM in A549 and HCC-44 cells, respectively. For tamarixetin, the IC 50 values were 19.6 and 20.3 µM in A549 and HCC-44 cells, respectively. These results were many-fold lower than the respective values for quercetin (72.2 and 107.6 µM for A549 and HCC-44 cells, respectively). Based on the activation of caspase family members, both metabolites induced apoptotic cell death in the tested cell lines, predominantly via the extrinsic pathway in A549 cells and in both intrinsic and extrinsic pathways in HCC-44 cells. As A549 and HCC-44 lines were originally established from a male and female patient, current data may suggst some gender differences in the action of quercetin derivatives. Addition of a methyl group in the 3'-or 4'-position of the B-ring of quercetin significantly increased the anticancer activity of this flavonol towards lung adenocarcinoma cells, which demonstrated that these compounds may be considered as potential novel candidates for the development of future chemotherapeutics in the fight against lung cancer.

Chemical Constituent Profiling of Phyllostachys heterocycla var. Pubescens with Selective Cytotoxic Polar Fraction through EGFR Inhibition in HepG2 Cells

“…According to the literature, 4-keto-pinoresinol was reported to be active against SK-Mel-2, B16F1, ovarian cancer SKOV-3, CaoV-3, and cervical cancer HeLa cell lines cycle [ 17 ]. Tamarixetin was previously reported to possess cytotoxic action against A-549 and HCC-44 lung adenocarcinoma cells, gastric carcinoma (AGS), skin melanoma (B16F10), brain carcinoma (C6), epitheliod cervix carcinoma (HeLa) cells, MCF-7 and HCT-116 cells [ 18 , 19 , 20 ]. Additionally, 3,4-dihydrozybenzoic acid was also reported to cause apoptosis on human breast cancer MCF-7 cell, lung cancer A-549 cell, HepG2 cell, cervix HeLa cell, prostate cancer LNCaP cell, and A549 human lung cancer [ 21 , 22 , 23 ].…”

Chemical composition and antioxidant, cytotoxic, and insecticidal potential of Valeriana alliariifolia in Turkey

“…It was reported cytotoxic against MCF-7 cells (70), and induced apoptosis in HepG2 cells (71). Methylquercetin was reported for antimigration and antiproliferative activities(72), while Sak et al (73) reported high cytotoxicity of its analogues 3'-O-methylquercetin Unknown -The major compounds are written in bold and 4'-O-methylquercetin against A549 and HCC-44 cell lines. Both analogues exhibited higher activity (IC 50 of 26.6 µmol/L and 19.6 µmol/L against A549 and 15.9 µmol/L and 20.3 µmol/L against HCC-44, respectively) than quercetin (72.2 µmol/L and 107.6 µmol/L, respectively).…”

Isorhamnetin Induces Cell Cycle Arrest and Apoptosis Via Reactive Oxygen Species-Mediated AMP-Activated Protein Kinase Signaling Pathway Activation in Human Bladder Cancer Cells

“…In addition, the anti-cancer effects of isorhamnetin in various cancer cell lines have been shown to involve the death receptor (DR)-dependent extrinsic and/or mitochondria-dependent intrinsic pathways [19,24,27,28,29,30,31], which are representative apoptosis inducing pathways. It was also found that the anti-cancer effect of isorhamnetin was accompanied by the disturbance of various cellular signaling pathways [20,25,32].…”