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Extraction, isolation and characterisation of antitumor principle, alpha-hederin, from the seeds of Nigella sativa.

We have previously reported the in vitro cytotoxic activity of column fraction 5 (CC-5) of an ethanolic extract of Nigella sativa seeds. In this study, the effect of CC-5 was evaluated for its in vivo antitumor activity against i.p. (intraperitoneally) implanted murine P388 leukemia and s.c. (subcutaneously) implanted LL/2 (Lewis lung carcinoma) cells in BDF1 mice (C57BL/6 x DBA/2 mice). CC-5 at doses of 200 and 400 mg/kg b.w. prolonged the life span of these mice by 153% compared to DMSO-treated control mice. The antitumor activity of a 21-day treatment of CC-5 against s.c. implanted LL/2 was tested in mice using four experimental protocols as described in the methods. In protocols C and D, CC-5 at a dose of 400 mg/kg b.w. produced significant tumor inhibition rate (TIR) values of 60% (P < 0.001) and 70% (P < 0.001) respectively. Alpha-hederin, a triterpene saponin isolated from CC-5, when given i.p. for 7 days at doses of 5 and 10 mg/kg b.w. to mice with formed tumors, produced significant dose-dependent TIR values of 48% (P < 0.05) and 65% (p < 0.01) respectively on day 8 and 50% (P < 0.01) and 71% (P < 0.001), respectively, on day 15, compared to 81% (P < 0.01) on day 8 and 42% (P < 0.01) on day 15 in the cyclophosphamide (CP)-treated group. The underlying mechanism(s) of antitumor activity of alpha-hederin remain to be established.