Limits...
Newly synthesized anticancer drug HUHS1015 is effective on malignant pleural mesothelioma.

Kaku Y, Nagaya H, Tsuchiya A, Kanno T, Gotoh A, Tanaka A, Shimizu T, Nakao S, Tabata C, Nakano T, Nishizaki T - Cancer Sci. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.

Show MeSH

Related in: MedlinePlus

Real-time RT-PCR analysis of NCI-H2052 cells treated with HUHS1015 (15 μM) or paclitaxel (15 μM) for periods of time as indicated. The mRNA quantity for each gene was calculated from the standard curve made by amplifying different amounts of the GAPDH mRNA, and normalized by regarding the average of independent basal mRNA quantity at 0 h as 1. In the graphs, each point represents the mean (±SEM) ratio relative to basal mRNA levels (n = 4 independent experiments).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4317914&req=5

fig05: Real-time RT-PCR analysis of NCI-H2052 cells treated with HUHS1015 (15 μM) or paclitaxel (15 μM) for periods of time as indicated. The mRNA quantity for each gene was calculated from the standard curve made by amplifying different amounts of the GAPDH mRNA, and normalized by regarding the average of independent basal mRNA quantity at 0 h as 1. In the graphs, each point represents the mean (±SEM) ratio relative to basal mRNA levels (n = 4 independent experiments).

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.


Newly synthesized anticancer drug HUHS1015 is effective on malignant pleural mesothelioma.

Kaku Y, Nagaya H, Tsuchiya A, Kanno T, Gotoh A, Tanaka A, Shimizu T, Nakao S, Tabata C, Nakano T, Nishizaki T - Cancer Sci. (2014)

Real-time RT-PCR analysis of NCI-H2052 cells treated with HUHS1015 (15 μM) or paclitaxel (15 μM) for periods of time as indicated. The mRNA quantity for each gene was calculated from the standard curve made by amplifying different amounts of the GAPDH mRNA, and normalized by regarding the average of independent basal mRNA quantity at 0 h as 1. In the graphs, each point represents the mean (±SEM) ratio relative to basal mRNA levels (n = 4 independent experiments).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317914&req=5

fig05: Real-time RT-PCR analysis of NCI-H2052 cells treated with HUHS1015 (15 μM) or paclitaxel (15 μM) for periods of time as indicated. The mRNA quantity for each gene was calculated from the standard curve made by amplifying different amounts of the GAPDH mRNA, and normalized by regarding the average of independent basal mRNA quantity at 0 h as 1. In the graphs, each point represents the mean (±SEM) ratio relative to basal mRNA levels (n = 4 independent experiments).
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.

Show MeSH
Related in: MedlinePlus