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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 1512745, 18 pages
Research Article

Oxidative Stress Triggered by Apigenin Induces Apoptosis in a Comprehensive Panel of Human Cervical Cancer-Derived Cell Lines

1Postgraduate Program in Bioscience and Physiopathology, Universidade Estadual de Maringá (UEM), Av. Colombo 5790, 87025-210 Maringá, PR, Brazil
2Clinical Cytology and STD Laboratory, Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá (UEM), Av. Colombo 5790, 87025-210 Maringá, PR, Brazil
3Postgraduate Program in Pharmaceutical Sciences, Laboratory of Research and Development of Drug Delivery Systems, Universidade Estadual de Maringá (UEM), Av. Colombo 5790, 87025-210 Maringá, PR, Brazil
4Postgraduate Program in Pharmaceutical Science-Clinical Analysis Area, Universidade de São Paulo (USP), Av. Lineu Prestes 580, 05508-900 São Paulo, SP, Brazil

Correspondence should be addressed to Marcia E. L. Consolaro; moc.liamg@oralosnoclem

Received 30 August 2016; Revised 13 December 2016; Accepted 18 December 2016; Published 16 January 2017

Academic Editor: Luciano Saso

Copyright © 2017 Raquel P. Souza et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Recently, the cytotoxic effects of apigenin (4′,5,7-trihydroxyflavone), particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and HPV 18-positive), and C33A (HPV-negative) cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT). Our results demonstrated that apigenin had a selective cytotoxic effect and could induce apoptosis in all cervical cancer cell lines which were positively marked with Annexin V, but not in HaCaT (control cells). Additionally, apigenin was able to induce mitochondrial redox impairment, once it increased ROS levels and H2O2, decreased the , and increased LPO. Still, apigenin was able to inhibit migration and invasion of cancer cells. Thus, apigenin appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV genotypes.