Paradoxical Effect of 2,3-Dimercapto-1-propanesulfonic Acid (DMPS) on Enhancing Antitumor Activity of Cisplatin in Ascites Sarcoma 180 Cells

Journal of Pharmacological Sciences

Kohei Sawaki²  Mitsuru Kawaguchi²  Hiroshi Maehashi¹  Migiwa Okubo²  Toshihiro Sato² 

[1] Department of Pharmacology, Matsumoto Dental University, Japan;Department of Pharmacology, Tokyo Dental College, Japan

关键词: 2;    3-dimercapto-1-propanesulfonic acid (DMPS);    meso-2;    3-dimercaptosuccinic acid (DMSA);    cisplatin;    sarcoma 180 cell;    antitumor activity;   

DOI  :  10.1254/jphs.09323FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(35)Cited-By(2)We investigated the enhancing effect of two metal-chelating compounds, 2,3-dimercapto-1-propanesulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA), on the antitumor activity of cisplatin (CDDP). In the in vivo experiments, DMPS showed a clear synergistic effect and significantly enhanced the antitumor activity of CDDP in terms of survival and life span in mice transplanted with ascites sarcoma 180 cells (S180 cells) at a dose of <100 μmol/kg, s.c., but not at a dose of >500 μmol/kg. On the other hand, DMSA did not enhance the antitumor activity of CDDP. DMPS (50 μmol/kg, s.c.) combined with CDDP also potently suppressed [3H]thymidine uptake in S180 cells implanted in mice, whereas DMSA did not. In the in vitro experiments, DMPS (10−6 to 10−5 M) produced a time- and dose-dependent decrease in intracellular Ca2+ concentrations ([Ca2+]i) in S180 cells and, in combination with CDDP, yielded a significant increase in intracellular platinum accumulation compared to that in cells treated with CDDP alone. These results indicate that DMPS used in combination with CDDP may be of considerable benefit in enhancing the cytotoxicity of CDDP in tumor cells, especially at a low dose. The results also suggest that the enhancing effect of DMPS is closely related to a decrease in [Ca2+]i and that the suitable dose and adequate administrational time of DMPS are important for its effective action.

【 授权许可】

Unknown