Phenanthroindolizidine alkaloids as cytotoxic substances in a Danaid butterfly, ideopsis similis, against human cancer cells

We previously reported the presence of cytotoxic substances in extracts of the Danaid butterfly, Ideopsis similis. In the present study, we isolated c ytotoxic substances against a human gastric cancer cell line, TMK-1, in I s imilis pupae, with an activity similar to that of the adult butterfly. The basic fraction, prepared from a methanol extract, accounted for 83% of the cytotoxic activity. Two major cytotoxic substances were purified by HPLC, a nd one was determined to be a new phenanthroindolizidine alkaloid, trans-()-3, 14 alpha -dihydroxy-6,7-dimethoxyphenanthroindolizidine (1), and the o ther a known compound, trans-(+)-3, 14 alpha -dihydroxy-4,6,7-trimethoxyphe nanthroindolizidine (2). The IC50 values for TMK-1 cells were 0.5 ng/mL and 0.7 ng/mL, respectively. These two compounds showed similar cytotoxic pote ntial with four other cancer cell lines including cervical, lung, and colon carcinomas and leukemia. Quantitative analyses indicated the presence of e ach of the two phenanthroindolizidine alkaloids at levels of 11-74 mug in e ach larva, pupa, or adult of I. similis. However, I was not detected in the leaves of Tylophora tanakae, a host plant for larvae of I. similis, and th e level of 2 (2 mug per gram of leaves) was far less than that in the larva e. Since the leaves of T. tanakae are known to contain various phenanthroin dolizidines, compounds 1 and 2 are presumably metabolically converted from such alkaloids in larvae of I. similis.