Hexane partition from Annona crassiflora Mart. promotes cytotoxity and apoptosis on human cervical cancer cell lines

• Published in: Investigational new drugs 2019-08, Vol.37 (4), p.602-615
• Main Authors: Silva, Viviane A. O., Alves, Ana Laura V., Rosa, Marcela N., Silva, Larissa R. V., Melendez, Matias E., Cury, Fernanda P., Gomes, Izabela N. F., Tansini, Aline, Longato, Giovanna B., Martinho, Olga, Oliveira, Bruno G., Pinto, Fernanda E., Romão, Wanderson, Ribeiro, Rosy I. M. A., Reis, Rui M.
• Format: Article
• Language: English
• Subjects: Adenosine diphosphate; Animals; Annona; Annona crassiflora Mart; Annona crassiflora Mart .Cytotoxity and cervical cancer cell line; Anticancer properties; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Biotechnology; Cancer; Caspase; Caspase-3; Caspase-9; Cell death; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell proliferation; Cell Survival - drug effects; Cervical cancer; Cervix; Chick Embryo; Cisplatin; Ciências Médicas; Cytotoxicity; Cytotoxity and cervical cancer cell lines; Deoxyribonucleic acid; Depolarization; DNA; DNA Damage; Female; Females; Hexane partition apoptosis; Hexanes - chemistry; Human papillomavirus; Humans; In vivo methods and tests; Medicina Básica; Medicine; Medicine & Public Health; Membrane potential; Mitochondria; Natural compounds; Neovascularization, Pathologic - drug therapy; Oncology; Partitions; Pharmacology/Toxicology; Plant Extracts - pharmacology; Plant Leaves; Poly(ADP-ribose) polymerase; Preclinical Studies; Proteasomes; Ribose; Science & Technology; Solvents - chemistry; Studies; Tumor cell lines; Tumors; Ubiquitin; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - pathology
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-018-0657-y

Cervical cancer is the third most commonly diagnosed tumor type and the fourth cause of cancer-related death in females. Therapeutic options for cervical cancer patients remain very limited. Annona crassiflora Mart. is used in traditional medicine as antimicrobial and antineoplastic agent. However, little is known about its antitumoral properties. In this study the antineoplastic effect of crude extract and derived partitions from A. crassiflora Mart in cervical cancer cell lines was evaluated. The crude extract significantly alters cell viability of cervical cancer cell lines as well as proliferation and migration, and induces cell death in SiHa cells. Yet, the combination of the crude extract with cisplatin leads to antagonistic effect. Importantly, the hexane partition derived from the crude extract presented cytotoxic effect both in vitro and in vivo, and initiates cell responses, such as DNA damage (H2AX activity), apoptosis via intrinsic pathway (cleavage of caspase-9, caspase-3, poly (ADP-ribose) polymerase (PARP) and mitochondrial membrane depolarization) and decreased p21 expression by ubiquitin proteasome pathway. Concluding, this work shows that hexane partition triggers several biological responses such as DNA damage and apoptosis, by intrinsic pathways, and was also able to promote a direct decrease in tumor perimeter in vivo providing a basis for further investigation on its antineoplastic activity on cervical cancer. This study was supported by grants from the FINEP (MCTI/FINEP/MS/SCTIE/DECIT-01/2013 -FPXII-BIOPLAT), CAPES, FAPEMIG, UFSJ and Barretos Cancer Hospital, all from Brazil.