Abstract
Cancer cells have the unique ability to overcome natural defense mechanisms, undergo unchecked proliferation and evade apoptosis. While chemotherapeutic drugs address this, they are plagued by a long list of side effects and have a poor success rate. This has spurred researchers to identify safer bioactive compounds that possess chemopreventive and therapeutic properties. A wide range of experimental as well as epidemiological data encourage the use of dietary agents to impede or delay different stages of cancer. In the present study, we have examined the anti-ancer property of ubiquitous phytochemical quercetin by using cell viability assay, flow cytometry, nuclear morphology, colony formation, scratch wound assay, DNA fragmentation and comet assay. Further, qPCR analysis of various genes involved in apoptosis, cell cycle regulation, metastasis and different signal transduction pathways was performed. Proteome profiler was used to quantitate the expression of several of these proteins. We find that quercetin decreases cell viability, reduces colony formation, promotes G2-M cell cycle arrest, induces DNA damage and encourages apoptosis. Quercetin induces apoptosis via activating both apoptotic pathways with a stronger effect of the extrinsic pathway relying on the combined power of TRAIL, FASL and TNF with up-regulation of caspases and pro-apoptotic genes. Quercetin could inhibit anti-apoptotic proteins by docking studies. Further, quercetin blocks PI3K, MAPK and WNT pathways. Anticancer effect of quercetin observed in cell-based assays were corroborated by molecular biology studies and yielded valuable mechanistic information. Quercetin appears to be a promising candidate with chemopreventive and chemotherapeutic potential and warrants further research.
Highlights
Cancer is one of the foremost causes of mortality across the world
The effect of quercetin on the viability of HeLa cells was determined by treating the cells with different concentrations of quercetin and evaluating the cell viability using MTT assay
HeLa cells when treated with increasing concentrations of quercetin (1–150 μM) for 24 and 48 h showed significant growth inhibition in a dose- and time-dependent manner
Summary
Cancer is one of the foremost causes of mortality across the world. Conventional cancer therapies lead to severe side effects, resulting in poor quality of life for the patient [1]. Extensive epidemiological evidences suggest that a diet of fruit and vegetables can prevent a range of human cancers and are associated with a decreased risk of cancer-related mortality [2,3,4,5,6,7]. Dietary polyphenols exhibit anti-inflammatory, immunomodulatory, antioxidant and pro-apoptotic properties and modulate cell signaling pathways that effectively suppress various stages of carcinogenesis [8,9,10,11]. Earlier in vitro studies demonstrate anticancer effect of phytochemicals derived from fruits and vegetables like genistein, License 4.0 (CC BY)
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