Research Papers:

Synergistic anti-tumor effect of bullfrog sialic acid-binding lectin and pemetrexed in malignant mesothelioma

Toshiyuki Satoh, Takeo Tatsuta, Shigeki Sugawara, Akiyoshi Hara and Masahiro Hosono _

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Oncotarget. 2017; 8:42466-42477. https://doi.org/10.18632/oncotarget.17198

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Toshiyuki Satoh1,2, Takeo Tatsuta2, Shigeki Sugawara2, Akiyoshi Hara1 and Masahiro Hosono2

1Department of Clinical Pharmacotherapeutics, Tohoku Medical and Pharmaceutical University, Aobaku, Sendai, Miyagi 981-8558, Japan

2Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Aobaku, Sendai, Miyagi 981-8558, Japan

Correspondence to:

Masahiro Hosono, email: [email protected]

Keywords: malignant mesothelioma, apoptosis, cell cycle, sialic acid-binding lectin, combination treatment

Received: December 28, 2016     Accepted: April 06, 2017     Published: April 18, 2017


Malignant mesothelioma is an aggressive cancer with limited therapeutic options. Sialic acid-binding lectin isolated from Rana catesbeiana oocytes (cSBL) is a multifunctional protein with anti-cancer activity. The effects of pemetrexed, cisplatin, and cSBL were evaluated in mesothelioma and normal mesothelial cell lines. We evaluated cytotoxicity, apoptosis, caspase-3 cleavage and activation, cell proliferation, cell cycle arrest, and levels of cell cycle proteins in H28 cells treated with pemetrexed, cisplatin, and cSBL alone or in combination. Treatment with cSBL alone was cytotoxic to mesothelioma cells. The anti-cancer effect of cSBL was observed in a broader range of cell lines and exhibited greater cancer cell selectivity than pemetrexed or cisplatin. Combination treatment with pemetrexed + cSBL resulted in greater dose-dependent cytotoxicity than pemetrexed + cisplatin, the standard of care in mesothelioma. The synergistic effect of pemetrexed + cSBL was mediated by the cytostatic effect of pemetrexed and the cytotoxic effect of cSBL. It thus appears that cSBL has therapeutic potential for the treatment of mesothelioma.

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