MK615, a prospective anti-proliferative agent, enhances CD4/CD8 ratio after exposure to irradiation

Abstract

Purpose: Recently, it was found that MK615 possessed an anti-proliferative ability on treated cancer cells as a consequence of triterpenoid compounds. It is well known that radiation affects cellular-mediated immunity in cancer patients who are treated with radiotherapy. Similarly, the ability of triterpenoid compounds to enhance the cellular-mediated immunity has been observed. Therefore, in the present study, we attempted to investigate the effect of MK615 on both cancer cells and cellular-mediated immunity after irradiation.

Materials and methods: After mice were inoculated with mouse mammary carcinoma (FM3A) cells, they were categorised as follows: Non-treated, irradiated with 5 Gy, treated with 660 μg/day MK615 (MK615, an extract from the Japanese apricot) and lastly exposed to both irradiation and MK615. Afterward, mice were sacrificed and spleens were utilised to measure the cluster of differentiation 4 and 8 (CD4 and CD8) using flowcytometry. Simultaneously, in vitro study, human alveolar basal epithelial carcinomic (A549), mouse lymphoma (EL4) and FM3A cell lines were examined. Growth inhibition was assessed via colony, cell viability and apoptotic assays.

Results: The median survival was in favour of the MK615-treated group (26.1 ± 1.9 days) compared with non-treated group (22.3 ± 2.3 days) (p < 0.05). Approximately 50% reduction of the CD4/CD8 ratio was observed following the exposure to irradiation alone. However, this ratio was comparable between the non-treated and both MK615-treated groups. Additionally, only the dual treatment was associated with tumour volume reduction. In contrast, in vitro study showed that MK615 had no significant (p ≥ 0.1) effect on the selected cell lines with or without irradiation.

Conclusion: MK615 has a potential to reduce tumour volume and may normalise cellular-mediated immunity level following the exposure to irradiation.

Keywords:

• MK615
• irradiation
• CD4/CD8 ratio
• triterpenoids

Acknowledgments

We would like to thank Ms Masako Shin and Ms Sayuri Tanemoto for their technical assistance. This study was supported in part by Japanese Society for the Promotion of Science.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.