Cytotoxic Effect of the Her-2/Her-1 Inhibitor PKI-166 on Renal Cancer Cells Expressing the Connexin 32 Gene

Eriko Fujimoto; Tomohiro Yano; Hiromi Sato; Kiyokazu Hagiwara; Hiroshi Yamasaki; Sumiko Shirai; Keiko Fukumoto; Hiromi Hagiwara; Etsuko Negishi; Koichi Ueno

doi:10.1254/jphs.SCJ04009X

Short Communications

Cytotoxic Effect of the Her-2/Her-1 Inhibitor PKI-166 on Renal Cancer Cells Expressing the Connexin 32 Gene

Eriko Fujimoto, Tomohiro Yano, Hiromi Sato, Kiyokazu Hagiwara, Hiroshi Yamasaki, Sumiko Shirai, Keiko Fukumoto, Hiromi Hagiwara, Etsuko Negishi, Koichi Ueno

Author information

Eriko Fujimoto
Department of Geriatric Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Chiba University
Tomohiro Yano
Department of Food Science Research for Health, National Institute of Health and Nutrition
Hiromi Sato
Department of Geriatric Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Chiba University
Kiyokazu Hagiwara
Department of Food Science Research for Health, National Institute of Health and Nutrition
Hiroshi Yamasaki
Department of Cell Biology, Faculty of Science and Technology, Kwansei Gakuin University
Sumiko Shirai
Department of Food Science Research for Health, National Institute of Health and Nutrition
Keiko Fukumoto
Department of Food Science Research for Health, National Institute of Health and Nutrition
Hiromi Hagiwara
Department of Food Science Research for Health, National Institute of Health and Nutrition
Japan Human Sciences Foundation
Etsuko Negishi
Department of Geriatric Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Chiba University
Koichi Ueno
Department of Geriatric Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Chiba University

Keywords: connexin 32, PKI-166, renal cancer cell

JOURNAL FREE ACCESS

2005 Volume 97 Issue 2 Pages 294-298

DOI https://doi.org/10.1254/jphs.SCJ04009X

View "Advance Publication" version (February 5, 2005).

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Abstract

We have reported that connexin (Cx) 32 acts as a tumor suppressor gene in renal cancer cells partly due to Her-2 inactivation. Here, we determined if a Her-2/Her-1 inhibitor (PKI-166) can enhance the tumor-suppressive effect of Cx32 in Caki-2 cells from human renal cell carcinoma. The expression of Cx32 in Caki-2 cells was required for PKI-166-induced cytotoxic effect at lower doses. The cyctotoxicity was dependent on the occurrence of apoptosis and partly mediated by Cx32-driven gap junction intercellular communications. These results suggest that PKI-166 further supports the tumor-suppressive effect of the Cx32 gene in renal cancer cells through the induction of apoptosis.

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