Newly synthesized anticancer drug HUHS1015 is effective on malignant pleural mesothelioma.
Bottom Line: The newly synthesized naftopidil analogue HUHS1015 reduced cell viability in malignant pleural mesothelioma cell lines MSTO-211H, NCI-H28, NCI-H2052, and NCI-H2452, with the potential greater than that for the anticancer drugs paclitaxel or cisplatin at concentrations higher than 30 μM.HUHS1015 induced both necrosis and apoptosis of MSTO-211H and NCI-H2052 cells.HUHS1015 upregulated expression of mRNAs for Puma, Hrk, and Noxa in MSTO-211H and NCI-H2052 cells, suggesting HUHS1015-induced mitochondrial apoptosis.
Affiliation: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.Show MeSH
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Mentions: We finally examined the effect of HUHS1015 on NCI-H2052 cell proliferation using mice inoculated with NCI-H2052 cells. Intraperitoneal injection with HUHS1015 at a dose of 9.15 mg/kg, corresponding to approximately 25 μM, twice a week significantly inhibited NCI-H2052 cell growth compared with that for control mice without HUHS1015 (P < 0.001, Fisher's protected least significant difference test) (Fig. 7a). All the mice treated with HUHS1015 survived 8 weeks after the beginning of HUHS1015 injection (Fig. 7b) and HUHS1015 had no effect on body weight (Fig. 7c). In addition, we have not confirmed apparent side-effects of HUHS1015 throughout these experiments. These results indicate that HUHS1015 could exert its beneficial anticancer effect on malignant pleural mesothelioma.
Affiliation: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.