title: Synergic Effect ofα-Mangostin on the Cytotoxicity of Cisplatin in a Cervical Cancer Model.
abstract: Cervical cancer is the second leading cause of death among Mexican women. The treatment with cis-diamminedichloroplatinum (II) (CDDP) has some serious side effects.Alpha-mangostin (α-M), has a protective effect against CDDP-induced nephrotoxicity, as well as antioxidant, antitumor, and anti-inflammatory properties. Hence, we explored the in vitro and in vivo effect ofα-M on human cervical cancer cell proliferation when combined with CDDP. In vitro, The cytotoxic effect ofα-M and/or CDDP was measured by the 3-(3,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium assay. Meanwhile, apoptosis, reactive oxygen species (ROS) production, and the cell cycle were determined with flow cytometry. Forα-M+CDDP treatment, both a coincubation and preincubation scheme were employed. In vivo, xenotransplantation was performed in female athymic BALB/c (nu/nu) mice, and then tumor volume and body weight were measured weekly, whereasα-M interfered with the antiproliferative activity of CDDP in the coincubation scheme, with preincubation withα-M+CDDP showing significantly greater cytotoxicity than CDDP orα-M alone, significantly inhibiting average tumor volume and preventing nephrotoxicity. This effect was accompanied by increased apoptosis and ROS production by HeLa cervical cancer cells, as well as an arrest in the cell cycle. These results suggest thatα-M may be useful as a neoadjuvant agent in cervical cancer therapy.
authors.affiliation: División de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando #22, Apartado Postal 22026, Tlalpan, 14000 Mexico City, Mexico.
authors.forename: Jazmin M
authors.identifier: 0000-0002-5766-2684
authors.initials: JM
authors.lastname: Pérez-Rojas
authors.affiliation: División de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando #22, Apartado Postal 22026, Tlalpan, 14000 Mexico City, Mexico.
authors.forename: Raquel
authors.initials: R
authors.lastname: González-Macías
authors.affiliation: División de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando #22, Apartado Postal 22026, Tlalpan, 14000 Mexico City, Mexico.
authors.forename: Jaime
authors.initials: J
authors.lastname: González-Cortes
authors.affiliation: División de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando #22, Apartado Postal 22026, Tlalpan, 14000 Mexico City, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Jurado
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, 04510 Mexico City, Mexico.
authors.forename: José
authors.identifier: 0000-0001-6628-4411
authors.initials: J
authors.lastname: Pedraza-Chaverri
authors.affiliation: División de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando #22, Apartado Postal 22026, Tlalpan, 14000 Mexico City, Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: García-López
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D004347:Drug Interactions; D004357:Drug Synergism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D044004:Xanthones; D002945:Cisplatin; C021053:mangostin