The effect of the combination therapy with chlorophyllin, a glutathione transferase P1-1 inhibitor, and docetaxel on triple-negative breast cancer invasion and metastasis in vivo/in vitro

Abstract

Abstract The expression of glutathione S-transferase P1 (GSTP1) enzyme increases in cancer cells, leading to anticancer drug resistance. The antioxidant chlorophyllin has an inhibitory effect on GSTP1. In this study, we investigated the effect of chlorophyllin and its combined administration with the chemotherapeutic agent docetaxel on metastatic processes. For this purpose, both the 4T1 triple-negative breast cancer cell line and metastatic animal model were used. The MTT, flow cytometry, and wound healing assays were used to investigate cell viability, cell cycle, and cell migration, respectively. Total gelatinase activity, GST activity, and glutathione levels in cell and liver tissue lysates measured by colorimetric methods. Micrometastases were evaluated histochemically in liver tissue sections. As a result, the coadministration of chlorophyllin and docetaxel significantly inhibited cell migration in vitro. There was a significant decrease in the total gelatinase activity in vivo. We found that only combined treatment reduced the micrometastatic lesions in the liver tissues, though this reduction was not statistically significant. In conclusion, the coadministration of chlorophyllin and docetaxel may have a potential role in controlling metastatic processes by suppressing cell migration, gelatinase activity, and micrometastasis formation in triple-negative breast cancers. Graphical Abstract </jats:p