Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Research article

Anti-cancer effects of newly developed chemotherapeutic agent, glycoconjugated palladium (II) complex, against cisplatin-resistant gastric cancer cells

Mamoru Tanaka1, Hiromi Kataoka1*, Shigenobu Yano23, Hiromi Ohi4, Keisuke Kawamoto5, Takashi Shibahara5, Tsutomu Mizoshita1, Yoshinori Mori1, Satoshi Tanida1, Takeshi Kamiya1 and Takashi Joh1

Author Affiliations

1 Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

2 Graduate School of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0192, Japan

3 Office of Society-Academia Collaboration for Innovation, Kyoto University, Katsura, Nishikyo-ku, Kyoto, Japan

4 Department of Industrial Chemistry, Kinki Polytechnic College, 1778 Inaba-cho, Kishiwada, Osaka, 596-0103, Japan

5 Department of Chemistry, Okayama University of Science, 1-1Ridai-cho, Kita-ku, Okayama, 700-0005, Japan

For all author emails, please log on.

BMC Cancer 2013, 13:237  doi:10.1186/1471-2407-13-237

Published: 14 May 2013

Abstract

Background

Cisplatin (CDDP) is the most frequently used chemotherapeutic agent for various types of advanced cancer, including gastric cancer. However, almost all cancer cells acquire resistance against CDDP, and this phenomenon adversely affects prognosis. Thus, new chemotherapeutic agents that can overcome the CDDP-resistant cancer cells will improve the survival of advanced cancer patients.

Methods

We synthesized new glycoconjugated platinum (II) and palladium (II) complexes, [PtCl2 (L)] and [PdCl2 (L)]. CDDP-resistant gastric cancer cell lines were established by continuous exposure to CDDP, and gene expression in the CDDP-resistant gastric cancer cells was analyzed. The cytotoxicity and apoptosis induced by [PtCl2 (L)] and [PdCl2 (L)] in CDDP-sensitive and CDDP-resistant gastric cancer cells were evaluated. DNA double-strand breaks by drugs were assessed by evaluating phosphorylated histone H2AX. Xenograft tumor mouse models were established and antitumor effects were also examined in vivo.

Results

CDDP-resistant gastric cancer cells exhibit ABCB1 and CDKN2A gene up-regulation, as compared with CDDP-sensitive gastric cancer cells. In the analyses of CDDP-resistant gastric cancer cells, [PdCl2 (L)] overcame cross-resistance to CDDP in vitro and in vivo. [PdCl2 (L)] induced DNA double-strand breaks.

Conclusion

These results indicate that [PdCl2 (L)] is a potent chemotherapeutic agent for CDDP-resistant gastric cancer and may have clinical applications.

Keywords:
Glycoconjugated platinum (II) complex; Glycoconjugated palladium (II) complex; Cisplatin; Drug resistance; Gastric cancer