In Vitro and In Vivo Effects of Holotoxin A1 From the Sea Cucumber Apostichopus japonicus During Ionizing Radiation

Radiation therapy is one of the most important approaches to cancer therapy, but radiotoxicity to normal tissue is a serious limitation of this treatment. Compounds which are able to either sensitize cancer cells or protect normal cells to radiation are of great interest. The cytotoxicity of holotoxin A 1 and the effects of radiation against DLD-1 and HT-29 cells were measured by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. The effect of the combination of holotoxin A 1 with X-ray on colony formation of cancer cells was determined by the soft agar assay. The effect of holotoxin A 1 on the recovery of peripheral blood leukocyte number, mass, and cellularity of the lymphoid organs of irradiated mice, as well as on growth of murine Ehrlich solid carcinoma was studied. Holotoxin A 1 enhanced the sensitivity of colorectal carcinoma cells to radiation in vitro. Injection of holotoxin A 1 to mice led to an increase in the spleen endogenous colony number and peripheral blood leukocyte number, as well as the weight and cellularity of the lymphoid organs of the irradiated mice. Holotoxin A 1 in combination with X-ray radiation effectively inhibited the growth of Ehrlich solid carcinoma in vivo. Holotoxin A 1 is suggested to be a promising agent for improving the efficiency of radiotherapy.