Newly synthesized anticancer drug HUHS1015 is effective on malignant pleural mesothelioma

Our plain-English summary of Newly synthesized anticancer drug HUHS1015 is effective on malignant pleural mesothelioma, by Y. Kaku, H. Nagaya, A. Tsuchiya, et al (Cancer Science, 2014).

The study

• Authors: Y. Kaku, H. Nagaya, A. Tsuchiya, T. Kanno, A. Gotoh, A. Tanaka, T. Shimizu, S. Nakao, C. Tabata, T. Nakano, T. Nishizaki
• Journal: Cancer Science
• Published: 2014;105(7):883-9
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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. HUHS1015 clearly suppressed tumor growth in mice inoculated with NCI-H2052 cells. Taken together, the results of the present study indicate that HUHS1015 could be developed as an effective anticancer drug for treatment of malignant pleural mesothelioma.

© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

In plain English

This was a laboratory study using human malignant pleural mesothelioma cell lines and mice. It did not involve patients or measure asbestos exposure. The authors tested HUHS1015, a newly made chemical related to the drug naftopidil, on four mesothelioma cell lines (MSTO-211H, NCI-H28, NCI-H2052 and NCI-H2452) and compared it with the cancer drugs paclitaxel and cisplatin. HUHS1015 lowered cell survival more as the dose rose. The effect was drastic above 30 micromolar, and survival was almost 0% of untreated levels at 100 micromolar. Paclitaxel brought survival to 40–50% at 100 micromolar, and cisplatin had a much smaller effect than paclitaxel. In two cell lines, HUHS1015 appeared to cause both necrosis and apoptosis (two forms of cell death). It also raised messenger RNA levels for Puma, Hrk and Noxa. In mice carrying NCI-H2052 tumors (n = 6), twice-weekly injections significantly slowed tumor growth compared with control mice (P less than 0.001). All treated mice survived 8 weeks, and body weight was unaffected. The authors concluded that HUHS1015 could be developed as an effective anticancer drug for malignant pleural mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory experiments on human mesothelioma cell lines, plus an animal experiment in mice implanted with human mesothelioma cells
• Who was studied: Four human malignant pleural mesothelioma cell lines (MSTO-211H, NCI-H28, NCI-H2052, NCI-H2452) bought from ATCC. Male 6-week-old nude BALB/c-nu/nu mice were injected under the skin with NCI-H2052 cells (n = 6 mice reported in the figure legend).
• Exposure: No asbestos exposure was studied. The exposure was the experimental compound HUHS1015, a naftopidil analogue, compared with paclitaxel and cisplatin. Cells were treated at 1 to 100 micromolar for 24 hours. Mice received intraperitoneal HUHS1015 at 9.15 mg per kg (said to correspond to about 25 micromolar) twice a week, starting 1 week after tumor cells were implanted.
• Main results:
  • In all four cell lines, HUHS1015 had a drastic effect on cell survival above 30 micromolar. Survival reached almost 0% of untreated levels at 100 micromolar.
  • Paclitaxel reduced survival of all four cell lines to 40–50% of untreated levels at 100 micromolar. Cisplatin reduced survival much less than paclitaxel.
  • In NCI-H2052 and MSTO-211H cells, flow cytometry results (15 micromolar, 24 hours) suggested that HUHS1015 caused both necrosis and apoptosis.
  • HUHS1015 increased messenger RNA levels for Bax, Puma, Hrk and Noxa in NCI-H2052 cells, and for Puma, Hrk and Noxa in MSTO-211H cells. The authors interpreted this as suggesting mitochondria-mediated apoptosis.
  • In mice with NCI-H2052 tumors, HUHS1015 significantly inhibited tumor growth compared with control mice given salt solution (P less than 0.001, Fisher's protected least significant difference test; n = 6 mice).
  • All HUHS1015-treated mice survived 8 weeks after injections began. HUHS1015 had no effect on body weight. The authors reported no apparent side-effects.
• The authors' conclusion: The authors concluded that HUHS1015 could be developed as an effective anticancer drug for treatment of malignant pleural mesothelioma.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Cisplatin, Necrosis, Apoptosis.

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