The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition.

Abstract

With increasing use of plant-derived cancer chemotherapeutic agents, exploring the antiproliferative effects of phytochemicals has gained increasing momentum for anticancer drug design. The dietary phytochemical quercetin, modulates several signal transduction pathways associated with cell proliferation and apoptosis. The present study was undertaken to examine the effect of quercetin on cell viability, and to determine the molecular mechanism of quercetin-induced cell death by investigating the expression of Bcl-2 family proteins (Bcl-2, Bcl-xL, Mcl1, Bax, Bad, p-Bad), cytochrome C, Apaf-1, caspases, and survivin as well as the cell cycle regulatory proteins (p53, p21, cyclin D1), and NF-κB family members (p50, p65, IκB, p-IκB-α, IKKβ and ubiquitin ligase) in human cervical cancer (HeLa) cells. The results demonstrate that quercetin suppressed the viability of HeLa cells in a dose-dependent manner by inducing G2/M phase cell cycle arrest and mitochondrial apoptosis through a p53-dependent mechanism. This involved characteristic changes in nuclear morphology, phosphatidylserine externalization, mitochondrial membrane depolarization, modulation of cell cycle regulatory proteins and NF-κB family members, upregulation of proapoptotic Bcl-2 family proteins, cytochrome C, Apaf-1 and caspases, and downregulation of antiapoptotic Bcl-2 proteins and survivin. Quercetin that exerts opposing effects on different signaling networks to inhibit cancer progression is a classic candidate for anticancer drug design.

• Authors: R Vidya Priyadarsini, R Senthil Murugan, S Maitreyi, K Ramalingam, D Karunagaran, S Nagini
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 649 Issue 1-3 Pg. 84-91 (Dec 15 2010) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 20858478 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Apoptosis Regulatory Proteins
• Cell Cycle Proteins
• NF-kappa B
• Tumor Suppressor Protein p53
• Quercetin

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Cell Cycle Proteins (genetics, metabolism)
• Cell Membrane (drug effects, pathology)
• Cell Nucleus (drug effects)
• Cell Survival (drug effects)
• Down-Regulation (drug effects)
• Female
• G2 Phase (drug effects)
• HeLa Cells
• Humans
• Mitochondria (drug effects, enzymology)
• NF-kappa B (metabolism)
• Osmolar Concentration
• Quercetin (pharmacology)
• Signal Transduction (drug effects)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• Up-Regulation (drug effects)
• Uterine Cervical Neoplasms (drug therapy, metabolism, pathology)