In Vitro Cytotoxicity of a Novel Antitumor Antibiotic, Spicamycin Derivative, in Human Lung Cancer Cell Lines

摘要: Abstract Spicamycin (SPM), produced by Streptomyces alanosinicus , induces potent differentiation in a human leukemia cell line, HL60. One of the derivatives SPM (SPM-D), KRN5500, has wide range antitumor activity against cancer lines. We examined cytotoxicity SPM-D small and non-small lung lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colony assays. was active All three cisplatin (CDDP)-resistant established our laboratory (PC-9/CDDP, PC-14/CDDP, H69/CDDP) showed collateral sensitivity to with relative resistance values 0.43, 0.34, 0.32, respectively. Intracellular PC-14/CDDP 35% higher than that for PC-14 suggesting intracellular accumulation can explain at least PC-14/CDDP. On other hand, PC-9/CDDP cells, no increase observed, but conversion ratio metabolite (the amino nucleoside moiety spicamycin binding glycine, SAN-G) from evaluated TLC as compared parental PC-9 cells (45.5% versus 37%; PC-9). The increased metabolism could mechanism cisplatin-resistant To elucidate determinant SPM-D-induced cytotoxicity, we SPM-D-resistant lines, PC-9/SPM-D, PC-14/SPM-D, H69/SPM-D, exposing stepwise increases concentration. resistances these sublines were more 5000, 46.6, 37.8 times those concentration metabolite, SAN-G, found be decreased sublines. This result indicates SAN-G is one determinants cellular In conclusion, both drug may contribute sensitivity/resistance merit investigation.