Newly synthesized anticancer drug HUHS1015 is effective on malignant pleural mesothelioma

Yoshiko Kaku; Hisao Nagaya; Ayako Tsuchiya; Takeshi Kanno; Akinobu Gotoh; Akito Tanaka; Tadashi Shimizu; Syuhei Nakao; Chiharu Tabata; Takashi Nakano; Tomoyuki Nishizaki

doi:10.1111/cas.12429

Newly synthesized anticancer drug HUHS1015 is effective on malignant pleural mesothelioma

Cancer Sci. 2014 Jul;105(7):883-9. doi: 10.1111/cas.12429. Epub 2014 May 21.

Authors

Yoshiko Kaku¹, Hisao Nagaya, Ayako Tsuchiya, Takeshi Kanno, Akinobu Gotoh, Akito Tanaka, Tadashi Shimizu, Syuhei Nakao, Chiharu Tabata, Takashi Nakano, Tomoyuki Nishizaki

Affiliation

¹ Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.

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.

Keywords: Apoptosis; Bcl-2 family; HUHS1015; malignant pleural mesothelioma; synthetic anticancer compound.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aniline Compounds / pharmacology*
Animals
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Apoptosis Regulatory Proteins / genetics
Cell Line, Tumor / drug effects
Cell Survival / drug effects
Gene Expression Regulation, Neoplastic / drug effects
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / genetics
Lung Neoplasms / pathology
Male
Mesothelioma / drug therapy*
Mesothelioma / genetics
Mesothelioma / pathology
Mesothelioma, Malignant
Mice
Mice, Inbred BALB C
Pleural Neoplasms / drug therapy*
Pleural Neoplasms / genetics
Pleural Neoplasms / pathology
Propanolamines / pharmacology*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins c-bcl-2 / genetics
Up-Regulation / drug effects

Substances

1-(2-(2-methoxyphenylamino)ethylamino)-3-(naphthalene-1-yloxy)propan-2-ol
Aniline Compounds
Antineoplastic Agents
Apoptosis Regulatory Proteins
BBC3 protein, human
HRK protein, human
PMAIP1 protein, human
Propanolamines
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcl-2