Synergic Effect ofα-Mangostin on the Cytotoxicity of Cisplatin in a Cervical Cancer Model
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.