A promising effect of zerumbone with improved anti-tumor-promoting inflammation activity of miR-34a in colorectal cancer cell lines.

Cross-talk among inflammation and colorectal cancer cells is chiefly reported through a complex of cytokines, chemokines, and growth factors. MicroRNA performs strategic roles in controlling a variety of signaling cascades. miR-34a is known as a master regulator of tumor suppression. Combined application of different miRNA-based agents and chemotherapeutic drugs has been used to augment drug sensitivity and may reinforce the antitumor effect. A lot of studies specify a substantial increase in the effectiveness of combination therapies. The anti-inflammatory activity of Zerumbone (ZER) was investigated in many cancers. In this study the level of the inflammatory cytokines including CXCL-12 (SDF-1), CCL-2 (MCP-1), TGF-β and IL-33 has been measured in pmiR-34a-5p transfected and pmiR-34a-5p +ZER treated CRC cell lines (HCT-116 and SW48) by QRT-PCR and ELISA methods, respectively. The results showed that miR-34a could significantly inhibit cytokine expression in both cell lines for 48 and 72 h except SDF-1 which no inhibition was observed in SW48 cells. ZER suppressed SDF-1 for all three time points in both cell lines, while in SW48 cells IL-33 and TGF-β were inhibited in 72 h and in HCT-116 cells MCP-1 diminished for only 24 h and TGF-β diminished for all three times. Combination of both miR-34a and ZER suppressed TGF-β, SDF-1 and MCP-1 in HCT-116 cells in all time points while in SW48 cells, suppression of most cytokines was observed in 48 and 72 h. Furthermore Colony formation assay and scratch test were employed to detect changes of proliferation and migration in CRC transfected and treated cells. Generally, we found that miR-34a could considerably decrease the expression of inflammatory cytokines and the combination of ZER+ miR-34 boosted this effect. Moreover the migration and proliferation decreased in treated and transfected cells and this reduction was more severe in miR-34a +ZER treatment. It is important to note that in the case of cell resistance to each of these therapeutic agents, inhibition of cytokines can be compensated by another one.