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

Abstract

Abstract. 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 μ mol/ kg, s.c., but not at a dose of >500 μ mol/kg. On the other hand, DMSA did not enhance the antitumor activity of CDDP. DMPS (50 μ mol/kg, s.c.) combined with CDDP also potently suppressed [ 3 H]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 Ca 2+ concentrations ([Ca 2+ ] 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 [Ca 2+ ] i and that the suitable dose and adequate administrational time of DMPS are important for its effective action.

The anti-tumor activities of cerebrosides derived from sea cucumber <i>Acaudina molpadioides</i> and starfish <i>Asterias amurensis in vitro</i> and <i>in vivo</i>

“…A total of 10 6 S180 cells suspended in 0.2 mL PBS were injected into the BALB/c mice via the abdominal cavity 29 .…”

Tuning the metabolism of the anticancer drug cisplatin with chemoprotective agents to improve its safety and efficacy

“…Numerous studies with animal models or patients have demonstrated that chemoprotective agents, such as sodium thiosulfate (STS), 15 N -acetyl- l -cysteine (NAC), 15a,16 amifostine, 15c,17 sodium diethyldithiocarbamate, 10,15c,18 d -methionine, 9,19 l -methionine, 19a,20 l -glutathione (GSH), 21 cimetidine, 22 sodium salicylate, 23 l -carnosine, 24 2,3-dimercapto-1-propanesulfonic acid, 25 and procaineamide hydrochloride 26 can significantly reduce some of the severe toxic side-effects of CP. While amifostine is the only chemoprotective agent that has been specifically approved by the FDA for CP therapy, 27 STS and NAC have been approved for the treatment of cyanide poisoning and for acetaminophen overdose, while d -methionine is currently undergoing a phase 3 clinical trial to reduce noise-induced hearing loss.…”

Design, Synthesis, and Activity Evaluation of a New 5-fluorouracil Prodrug Containing an Asn-Gly-Arg(NO2)COOCH3 Tripeptide

“…The mice were sacrificed and the tumors in the armpit were weighed. The result was expressed through inhibition rate [20]:…”