Analyzing the AntiCancer and AntiMutagenic Properties of Dinactin, a Macrolide Antibiotic

Produced from Streptomyces, Dinactin is one of the most important macrolide antibiotics. Previous studies have found that dinactin exerts inhibiting the cancer stemness potential of lung cancer, making it a promising option for CRC therapy. In this study, we designed experiments to evaluate dinactin's inhibitory effects against two human colorectal cancer cells (HCT116 and HT29) and elucidate the mechanism of its anti-cancer effects. Finally, we provided the first ever investigation of the mutagenic and anti-mutagenic potentials of dinactin.

We studied the effects of dinactin as part of an anti-cancer approach using MTT test, clonogenic assay, wound healing assay, and transwell migration assay in HCT116 and HT29 cells. Mechanical studies were conducted using flow cytometry and Cell Death Detection ELISA. The mutagenic and anti-mutagenic properties were demonstrated using the in vitro cytokinesis-blocked micronucleus assay in V79 cells.

Dinactin was found to have dose-dependent inhibitory effects on the viability of HCT116 and HT29 cells with IC50 values of 1.6 ±0.4 and 35.0 ±14 nM, respectively. Furthermore, dinactin showed potent anti-proliferation, anti-migration, and anti-invasion activities and demonstrated similar activity to doxorubicin. Mechanically, treatment with dinactin resulted in increased DNA fragmentation and positive AnnexinV/FITC-PI staining, which demonstrated the induction of apoptosis by dinactin. From the results of the mutagenic assay, dinactin did not produce a significant increase in micronucleus frequency when compared with a negative control (p > 0.05). In order to verify dinactin's anti-mutagenic properties, a combination of MMC (a known mutagen) and dinactin were applied to V79 cells. Treatment with dinactin resulted in a significant decrease in the number of micronucleated cells.

Dinactin inhibits growth and alleviates the progression of CRC cells at nanomolar concentrations. This anti-CRC activity is mediated through the induction of apoptosis. Dinactin did not exhibit mutagenic effects and has the potential to reduce the mutagenic action of MMC.