Anticancer Activity of Chinese Medicinal Herbs
Smitha Devaram, Biotechnology and Drug Delivery Laboratory
Jun Shao, Department of Pharmacy and Administrative Sciences, College of Pharmacy and Health Sciences
Abstract: Purpose: Previous studies have shown an herbal formula of six herbs [Radix Ginseng, Radix Notoginseng, Radix Asparagi, Radix Atractyloidis Macrocephalae, Ganoderma japonicum, Poria cocos] is effective against melanoma in mice. The main objective of the present study is to further evaluate the anticancer activity of the herbal formula against leukemia. The secondary objective is to investigate its acute toxicity.
Methods: Aqueous extract of the herbal formula was prepared. The antiproliferative activity of the herbal extract and doxorubicin and their combination was tested against one mouse cancer cell line [L1210 (leukemia)], three human cancer cell lines [K562 (leukemia), MDA-MB-231(breast cancer), MCF7 (breast cancer)], one doxorubicin resistant cell line [CV60 human epidermoid carcinoma] and one human normal cell line [HEK293- renal cell line]. The acute toxicity study of the herbal extract was performed in C57BL/6 mice by oral gavage with the maximum applicable dose (MAD) in 200 µL, which was equal to 1333 mg of the raw herbal materials. The anticancer activity of the herbal extract was evaluated in C57BL/6 DBA/2 mice with L1210 leukemia. The mice were injected intraperitoneally with 0.45x107 L1210 cells. Then mice were randomized into five groups of eight each. Group 1- negative control; Group 2 and Group 3 - herbal extract at the dose of 3 g/kg (raw material) and 6 g/kg, respectively. Group 4 and Group 5 - i.v. with doxorubicin (15 mg/kg) in three divided doses. Group 5 was also given the food mixed with the herbal extract (3g/kg). The animals were observed for their survival time.
Results: The herbal extract was effective in inhibiting the growth of all the cancer cell lines in vitro with the IC50 values ranging from 5-11 mg/mL. The highest tested concentration (20 mg/ml) resulted in 80-95% growth inhibition for all the cancer cell lines. The IC50 values of doxorubicin were varying between 0.06 mg/L to 3 mg/L. The IC50 value of the herbal extract and doxorubicin against the normal cell line (HEK293) was 20 mg/mL and 0.03 mg/L, respectively. The ratio of IC50 against the cancer cells vs IC50 against the normal cells by the herbal extract and by doxorubicin was in the range of 0.25-0.55, and 2.33-100, respectively, which demonstrate that the antiproliferative activity of the herbal extract was more cancer selective. The combination of the herbal extract and doxorubicin showed additive or synergistic effect depending on the cell line. The in vivo toxicity study revealed that the oral administration of MAD did not cause any noticeable adverse effect. The in vivo anticancer studies showed that the treatment of the herbal extract can statistically significantly increase the survival time (p<0.05). Treatment with doxorubicin alone and combined with the herbal extract increased the survival time by 62% and 65%, respectively. The previous study showed that the herbal extract inhibited the melanoma growth by 40% in C57BL/6 mice. Thus it can be concluded that the anticancer activity of the herbal extract varies according to the tumor type.
Conclusion: The aqueous extract of the herbal formula was effective in inhibiting the cancer growth in vitro. The oral administration of the extract was safe up to a dose of 66.65 g/kg (raw materials). The herbal extract has different anticancer efficacy against leukemia and melanoma.