In Vitro Study of Landomycin E Antitumor Activity

Landomycin E (LE) was recently isolated from Streptomyces globisporus strain 1912 and its chemical structure was studied. However, its biological activity is still poorly understood. We performed in vitro investigation of antitumor activity of this new member of the angucyclin family of antibiotics. Dose-dependent effect of LE on growth and survival of different tumor cell lines was studied in comparison with such effect of other anticancer drugs (adriamycin, cisplatin, methotrexate, vincristine and fluorouracil). LE (2.5–10.0 μg/ml) inhibited growth of human colon adenocarcinoma cells of SW-480 line to a similar extent as adriamycin and stronger than fluorouracil, cisplatin and methotrexate did. IC 50 for LE was found to be 1.28 μg/ml for human breast carcinoma cells of MCF-7 line, 6.68 μg/ml for human breast carcinoma cells of T47D line, 3.3 μg/ml for human colon adenocarcinoma cells of SW-480 line, 6 μg/ml for human colon adenocarcinoma cells of HT-29 line, 5 μg/ml for human mouth adenocarcinoma cells of KB line, 1.75 μg/ml for mouse leukemia cells of L1210 line, 2.68 μg/ml for mouse transformed fibroblasts of L929 line, 2.04 μg/ml for mouse embryo fibroblasts of NIH-3T3 line, 15.04 μg/ml for mink lung epithelial cells of CCL-64 line, and 2.68 μg/ml for mouse monocytes/macrophages of J774.2 line. Apoptotic DNA fragmentation was elicited under LE effect in L1210 leukemia cells. Investigation of various tumor cell lines showed the appearance of different cytomorphological changes characteristic for apoptosis (condensation of cytoplasm and nucleus, nucleus fragmentation, development of multiple vacuoles in the cytoplasm, and appearance of apoptotic protrudings of plasma membrane), although other ways of LE-induced cell death cannot be also excluded. These data may be helpful for further elucidation of cellular and molecular mechanisms of LE antineoplastic action.