Kesara Na-Bangchang, Kanchana Ketsa-ard, Suchitra Wiwatwittaya, Sommai Thongprasert, Molvibha Vongsakul, Pornthipa Picha and Juntra Karbwang
There are strong evidences supporting folklore about medicine, in particular, those having a historical reputation as anticancer agents that represent promising candidates for chemotherapeutic research and development. The objective of the present study is to investigate the anticancer and immunostimulating activities of one Thai folkloric remedy for the treatment of cancer in vitro and in vivo. The cytotoxic activity of the remedy was investigatedin vitro in KB cells and in vivo in mammary cancer-bearing rat (induced by 7, 12 DMBA at a single oral dose of 150 mg/kg body weight) and in cervical cancer xenograft nude mouse models. Acute and subacute toxicity tests were performed following intraperitoneal and/or oral dose administration. In the rat model, 30 rats received a daily dose of distilled water (control group) or the remedy at a daily dose of 1,500 mg/kg body weight (treated group) by intragastric gavage. In the mice model, 16 mice received a daily dose of distilled water (control group) or intraperitoneal injection of two doses of 1 mg/kg body weight mitomycin C (positive control) or the remedy at a daily dose of 2,580 mg/kg body weight (treated group) by intragastric gavage for 60 days. Splenic mononuclear cells from nude mice treated with the remedy at a dose of 2,580 mg/kg body weight/day for 1, 2, and 3 weeks were investigated for their NK cell activities by a 4 h 51Cr release assay, in comparison with that of the corresponding control groups. Based on the criteria for cytotoxic activity proposed by the National Cancer Institute of USA (IC50 < 30 mg/ml), the cytotoxic activity of the remedy (IC50 > 100 mg/ml) was considered weak (IC50 > 100 mg/ml). The remedy was well tolerated in both acute and subacute toxicity tests. The remedy was shown to exert significant anticancer activity in both animal models. In the rat model, the 180-day survival rates of rats in the treated group (53.57%) were significantly higher than the untreated group (53.57 vs. 6.89%, p < 0.01) and the survival time was significantly longer than that of the untreated group (173 (133-220) vs. 119 (90-143) days, p < 0.01]. In addition, the lung metastasis rate was significantly lower in the treated group (10.17vs. 20.69%). In mice model, significant inhibition of tumor volume was observed in mice treated with the extract from day 10 to day 60 (T/C =50-75%, with maximum activity on day 28) compared with the control (p < 0.05). The NK cell cytotoxic activity (%) in mice treated with the remedy for 1 or 2 weeks was significantly increased (by about 8.26-57.97% and 13.3-42.7%, respectively) compared with the control. The remedy may exert its anticancer activity by acting as an immunostimulating agent through activating NK cell activity.
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