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: To see the effect of HUHS1015 on expression of Bcl-2 family mRNAs, real-time RT-PCR was carried out in NCI-H2052 and MSTO-211H cells. For NCI-H2052 cells, HUHS1015 (15 μM) upregulated expression of mRNAs for Bax, Puma, and Noxa in a bell-shaped treatment time (2–12 h)-dependent manner, reaching its peak at 6 h (Fig. 5b,d,f), and Hrk in a treatment time-dependent manner (Fig. 5e), whereas expression of mRNAs for Bad, Bid, Bcl-2, Bcl-XL, and Mcl-1 was not affected (Fig. 5a,c,g–i). For MSTO-211H cells, HUHS1015 (15 μM) upregulated expression of mRNAs for Puma, Hrk, and Noxa in a treatment time (2–12 h)-dependent manner (Fig. 6d–f), but no remarkable effect on expression of mRNAs for Bad, Bax, Bid, Bcl-2, Bcl-XL, or Mcl-1 was obtained (Fig. 6a–c,g–i). Collectively, these results suggest that HUHS1015 induces mitochondria-mediated apoptosis of NCI-H2052 and MSTO-211H cells.
Affiliation: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.