title: Oxidative Stress Triggered by Apigenin Induces Apoptosis in a Comprehensive Panel of Human Cervical Cancer-Derived Cell Lines.
abstract: 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 Δψm, 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.
authors.affiliation: Postgraduate Program in Bioscience and Physiopathology, Universidade Estadual de Maringá (UEM), Av. Colombo 5790, 87025-210 Maringá, PR, Brazil; Clinical Cytology and STD Laboratory, Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá (UEM), Av. Colombo 5790, 87025-210 Maringá, PR, Brazil.
authors.forename: Raquel P
authors.initials: RP
authors.lastname: Souza
authors.affiliation: Clinical Cytology and STD Laboratory, Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá (UEM), Av. Colombo 5790, 87025-210 Maringá, PR, Brazil.
authors.forename: Patrícia de S
authors.identifier: 0000-0002-0116-2189
authors.initials: PS
authors.lastname: Bonfim-Mendonça
authors.affiliation: Postgraduate Program in Bioscience and Physiopathology, Universidade Estadual de Maringá (UEM), Av. Colombo 5790, 87025-210 Maringá, PR, Brazil; Clinical Cytology and STD Laboratory, Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá (UEM), Av. Colombo 5790, 87025-210 Maringá, PR, Brazil.
authors.forename: Fabrícia
authors.initials: F
authors.lastname: Gimenes
authors.affiliation: Postgraduate Program in Bioscience and Physiopathology, Universidade Estadual de Maringá (UEM), Av. Colombo 5790, 87025-210 Maringá, PR, Brazil.
authors.forename: Bianca A
authors.initials: BA
authors.lastname: Ratti
authors.affiliation: Postgraduate 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.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Kaplum
authors.affiliation: Postgraduate 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.
authors.forename: Marcos L
authors.initials: ML
authors.lastname: Bruschi
authors.affiliation: Postgraduate 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.
authors.forename: Celso V
authors.initials: CV
authors.lastname: Nakamura
authors.affiliation: Postgraduate Program in Bioscience and Physiopathology, Universidade Estadual de Maringá (UEM), Av. Colombo 5790, 87025-210 Maringá, PR, Brazil; Postgraduate 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.
authors.forename: Sueli O
authors.identifier: 0000-0001-9303-0804
authors.initials: SO
authors.lastname: Silva
authors.affiliation: Postgraduate Program in Pharmaceutical Science-Clinical Analysis Area, Universidade de São Paulo (USP), Av. Lineu Prestes 580, 05508-900 São Paulo, SP, Brazil.
authors.forename: Silvya S
authors.initials: SS
authors.lastname: Maria-Engler
authors.affiliation: Postgraduate Program in Bioscience and Physiopathology, Universidade Estadual de Maringá (UEM), Av. Colombo 5790, 87025-210 Maringá, PR, Brazil; Clinical Cytology and STD Laboratory, Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá (UEM), Av. Colombo 5790, 87025-210 Maringá, PR, Brazil; Postgraduate Program in Pharmaceutical Science-Clinical Analysis Area, Universidade de São Paulo (USP), Av. Lineu Prestes 580, 05508-900 São Paulo, SP, Brazil.
authors.forename: Marcia E L
authors.identifier: 0000-0001-9102-4865
authors.initials: ME
authors.lastname: Consolaro
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D002583:Uterine Cervical Neoplasms
chemical_list: D000970:Antineoplastic Agents; D047310:Apigenin