46P - Effect of coadministration of antioxidant chlorophyllin with docetaxel on invasion and metastasis in triple-negative breast cancer in vivo/in vitro

Background

The drug resistance against chemotherapy and high metastasis rate in triple-negative breast cancer reduce the success of breast cancer treatment. Glutathione S-transferase P1 enzyme (GSTP1) expression increases in cancer cell lines and leads to the development of drug resistance against chemotherapy. The antioxidant chlorophyllin is shown to have an inhibitory effect on GSTP1. The purpose of this study is to investigate the effects of GSTP1 inhibitor chlorophyllin and/or its coadministration with anticancer drug docetaxel on metastatic processes in vitro/in vivo in the 4T1 triple-negative breast cancer cell line and animal model.

Methods

Cell viability, cell cycle, and cell migration were investigated by MTT test, flow cytometry, and wound closure assay, respectively. Matrix metalloproteinase 9 (MMP-9) expression, causing invasion, was determined by Western Blot in the 4T1 cell line and tissue samples. Further, total gelatinase enzyme activity was also detected by gelatin degradation assay. Total GST enzyme activity and glutathione levels of tissue were investigated by colorimetric methods. Micrometastatic foci in liver tissue sections were evaluated by histochemistry.

Results

As a result, coadministration of chlorophyllin and docetaxel significantly inhibited cell migration in vitro. Chlorophyllin significantly reduced the expression of MMP-9 in the tissue samples, and this effect was higher when it is coadministered with docetaxel. In coadministration, a significant decrease was observed in the total gelatinase activity in vivo. It was also determined that chlorophyllin increased in vivo total glutathione levels and decreased GST enzyme activity. Finally, the micrometastases in the liver were reduced by coadministration.

Conclusions

Our results suggest that the coadministration of chlorophyllin and docetaxel may have a potential role in the control of metastatic processes by suppressing cell migration and invasion which is mainly characterized by gelatinase enzyme expression & activity.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Hacettepe University Scientific Research Projects Coordination Unit.

Disclosure

All authors have declared no conflicts of interest.