Antitumor Activity and Cross-Resistance of A Novel Podophyllotoxin Analog, NK611, to Human Small-Cell Lung Cancer Cell Lines

We compared the antitumor activity of etoposide, teniposide, and a novel podophyllotoxin analog, NK611, with the MTT assay using a human small-cell lung cancer cell line, SBC-3, with 1-hour drug exposure. The ratio of the area under the curve (AUC) to the 50% inhibitory concentration (IC50) of each drug was used as an index of antitumor activity. The AUC/IC50 ratio of NK611 was 13.6, which was comparable with etoposide (13.5), but inferior to teniposide (90.1). The degree of cross-resistance of teniposide and NK611 to etoposide was investigated using an etoposide-resistant subline, SBC-3/ETP, which was 17.4-fold more resistant to etoposide than the parent cell line, SBC-3. The SBC-3/ETP cell line was 7.64-fold more resistant to teniposide than the SBC-3 cell line. Nevertheless, the resistant cell line was only 2.64-fold more resistant to NK611 than the parent cell line. These observations suggest that NK611 may be beneficial in the treatment of etoposide-resistant small cell lung cancer.