Co-SLD suppressed the growth of oral squamous cell carcinoma via disrupting mitochondrial function

Abstract

To evaluate the safety and efficacy of novel cobalt complex with sulindac (Co-SLD), the zebrafish and oral squamous cell carcinoma CAL27 were investigated in the present study. The developmental toxicity of Co-SLD ranging from 5 to 20 μM was determined by exposure to 3–144-h post-fertilization (hpf) zebrafish. Our data showed that Co-SLD did not cause to the appreciable toxicity at low concentration (5 and 10 μM). A remarkable toxicity was observed at high concentration (20 μM), including increased mortality and malformation, delayed hatchability, reduced heart rate as well as suppressed behaviour. With regard to the antitumor activity of Co-SLD, inhibited cell growth and migration capability were outstandingly observed in oral squamous cell carcinoma treated with 10 and 20 μM Co-SLD, which could be mainly attributed to the Co-SLD-elicited mitochondrial damage as marked by the depression of mitochondrial membrane potential, ROS accumulation and ATP depletion. Furthermore, administration of 10 μM Co-SLD was an optimal concentration not only to avoid the normal tissue toxicity, but also to enhance the killing of cancer cells via disrupting mitochondrial dysfunction. Taken together the above results demonstrated the desirable response of oral squamous cell carcinoma to Co-SLD.

Keywords:

• Co-SLD
• oral squamous cell carcinoma
• antitumor activity
• zebrafish
• embryonic toxicity
• mitochondrial dysfunction

Disclosure statement

The authors confirm that this article content has no conflict of interest.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 11575262 and 11605255), and Scientific Technology Research Projects of Gansu Province (18JR3RA377 and 17JR5RA315).