Induction of metastatic cervical cancer via HeLa cell xenograft in female Wistar rats: Modulatory effects of Yoyo Bitters

Abstract

Yoyo Bitters (YYB) is a herbal formulation reported to reduce cellular free radical damage, remove harmful toxins, etc. Here, we report the investigation of the therapeutic activity of YYB on HeLa cell xenografted rats. Thirty rats were distributed into: control, dexamethasone, HeLa, HeLa + dose (0.2 mL/kg YYB), and HeLa + dose2 (0.6 mL/kg YYB) groups. Following immunosuppression, the rats were xenografted with HeLa cells to induce metastatic cervical cancer. The rats were administered YYB daily for two weeks. Whole blood was obtained for haematological analyses (total white blood cells (WBC), lymphocytes (LYM), neutrophils (NEUT), platelets (PLT), mid-range absolute (MID) counts) and to determine total protein (TP) levels. Serum activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and levels of reduced glutathione (GSH), lipid peroxidation (LPO) and nitric oxide (NO) were determined spectrophotometrically. The expression levels of vimentin, cytokeratin, Bax and Bcl-2 proteins were determined immunohistochemically. HeLa cell xenografts caused a significant decrease in the levels of WBC, LYM and PLT, but the levels of MID and NEUT increased significantly (p < 0.05). YYB modulated WBC, LYM, PLT, MID, and NEUT to levels that are not significantly (p > 0.05) different from the negative control. Furthermore, YYB dose-dependently modulated the activities of SOD, CAT and GST. In addition, the significantly induced levels of LPO and NO in HeLa cell xenograft group were abated by YYB. Immunohistochemically, YYB modulated the levels of all proteins assessed with an inclination toward apoptosis. Yoyo Bitters showed potential therapeutic activity via the modulation of antioxidant status.