Rhizoxin is a new macrocyclic
lactone isolated from the fungus Rhizopus chinensis. In an attempt to predict the effectiveness of
rhizoxin in the treatment of
lung cancer, we compared the antitumor activity of
rhizoxin with those of
cisplatin and
etoposide using four
small cell lung cancer (SCLC) cell lines, SBC-2, -3, -4, and -7, and two
non-small cell lung cancer (NSCLC) cell lines, ABC-1 and EBC-1. The concentrations producing 50% inhibition of the growth of these cell lines (IC50) for each
drug were obtained by MTT assay. The IC50 of
rhizoxin for these cell lines ranged 0.408 nM to 1.56 nM, which were significant lower than those of
cisplatin (660 nM to 16,300 nM) and
etoposide (275 nM to 31,300 nM). The ratio of IC50 for the most sensitive cell line, SBC-3, to that for the most resistant cell line was less than 4-fold in
rhizoxin, in contrast to more than 20-fold in
cisplatin and 100-fold in
etoposide. Cross-resistance of
rhizoxin to
cisplatin and
etoposide was investigated using a
cisplatin-resistant SCLC subline, SBC-3/CDDP, and an
etoposide-resistant SCLC subline, SBC-3/ETP. Of interest, the parent cell line, and the resistant sublines were equally sensitive to
rhizoxin, indicating
rhizoxin being non-cross-resistant to
cisplatin and
etoposide. In conclusion,
rhizoxin may be beneficial in the salvage
chemotherapy of
drug-resistant SCLC and non-SCLC.