Synergic Effect of α‐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 of α-M on human cervical cancer cell proliferation when combined with CDDP. In vitro, The cytotoxic effect of α-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. For α-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, whereas α-M interfered with the antiproliferative activity of CDDP in the coincubation scheme, with preincubation with α-M+CDDP showing significantly greater cytotoxicity than CDDP or α-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 that α-M may be useful as a neoadjuvant agent in cervical cancer therapy.

α‐Mangostin attenuates stemness and enhances cisplatin‐induced cell death in cervical cancer stem‐like cells through induction of mitochondrial‐mediated apoptosis

“…Our previous study demonstrates that α‐mangostin can activate reactive oxygen species signaling and induce apoptosis of HeLa cell (Lee et al, 2017), suggesting that α‐mangostin has potential anticancer activity against cervical cancer cells. Similarly, α‐mangostin has been reported to show a synergistic effect on cisplatin‐induced cytotoxicity on the HeLa cell in vitro and in vivo (Perez‐Rojas et al, 2016). In addition, α‐mangostin also has a protective effect on cisplatin‐induced kidney injury (Perez‐Rojas et al, 2009).…”

Activation of the P2X7receptor in midbrain periaqueductal gray participates in the analgesic effect of tramadol in bone cancer pain rats

“…Cell viability was estimated by MTT ((3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)) assay as described previously. 37 …”

Xanthones and Cancer: from Natural Sources to Mechanisms of Action

“…The structural diversity and biological aspects of xanthones make these secondary metabolites attractive to researchers, in the search for new and potent anticancer drug candidates . In recent years, studies on the anticancer and anti‐inflammatory activities of xanthones have shown significant results, mostly demonstrating their efficacy and low toxicity in normal cells …”

“…[194] In recent years, studies on the anticancer and anti-inflammatory activities of xanthones have shown significant results, mostly demonstrating their efficacy and low toxicity in normal cells. [195,196] Table 2. Overview of the main synthetic routes to obtain xanthone derivatives.…”