Vesnarinone and glucocorticoids cooperatively induce G1 arrest and have an anti-tumour effect on human non-small cell lung carcinoma cells grown in nude mice.
Vesnarinone, an oral cardiotonic, inhibited the growth of several human non-small cell lung carcinoma cell lines, and its anti-proliferative effects in vitro and in vivo were greatly enhanced by combination with glucocorticoids, but not other steroids. Simultaneous treatment with vesnarinone and dexamethasone is the most effective to evoke the synergistic effect in the growth inhibition of lung carcinoma EBC-1 cells. Dexamethasone and other glucocorticoids induced morphological changes in EBC-1 cells and these agents together with vesnarinone induced alkaline phosphatase activity, which is a typical marker of type II pneumocyte maturation. This treatment arrested the growth of the cells at the G1 phase, indicating that this treatment is cytostatic rather than cytotoxic. These results suggest that vesnarinone plus glucocorticoid might be useful in lung cancer therapy.
Honma
Y
Y
Department of Chemotherapy, Saitama Cancer Center Research Institute, Ina, Japan.
Yamamoto-Yamaguchi
Y
Y
Kanatani
Y
Y
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D016193:G1 Phase / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005938:Glucocorticoids; D011719:Pyrazines; D011804:Quinolines; D016160:Retinoblastoma Protein; C041667:vesnarinone; D003907:Dexamethasone; D000469:Alkaline Phosphatase