ABSTRACT
Taiwanofungus camphoratus has been reported to have antitumor effects against various cancer cells. The aim of this study was to investigate the direct inhibitory effect of By-1 (3-isobutyl-l-methoxy-4-[4'-(3-methylbut-2-enyloxy)phenyl]-1H-pyrrole-2,5-dione), a compound from spent broth from submerged cultures of T. camphoratus, on human lung adenocarcinoma cells and to determine the molecular mechanism underlying this effect. The growth-inhibitory assay and colony formation assay showed that cell viability was significantly decreased. A By-1 concentration of 300 µmol/L caused 73.55% cell death and at a concentration of 240 µmol/L led to a 58% reduction in the number of colonies. The wound-healing assay showed that the distance of migration was 0.3 times shorter than that of untreated cells. Flow cytometry revealed that By-1 could suppress DNA synthesis, cause cell cycle arrest at the S phase, and induce apoptosis in a reactive oxygen species-dependent manner. Furthermore, the expression of caspase-3 and P53 was 4 times higher than that in untreated cells, and the antiapoptotic protein Bcl-2 was decreased 2 times compared with the protein in untreated cells. It is interesting to note that apoptosis and autophagy were both induced during treatment with By-1, and autophagy inhibition decreased cell proliferation. By-1 potently inhibited the growth of SPCA-1 cells by inducing cell cycle arrest and apoptosis. The combination of proapoptosis agents and antiautophagy agents could effectively enhance anticancer efficacy, which may be a new strategy in treating non-small cell lung cancer.
