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

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 effects 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. Western blot analysis was used to evaluate the expression of matrix metalloproteinase 9 (MMP-9). Total gelatinase activity, GST activity, and glutathione levels in cell and liver tissue lysates measured by colorimetric methods. Micrometastases were evaluated in liver tissue sections histochemically. As a result, the coadministration of chlorophyllin and docetaxel inhibited cell migration in vitro. The single administration of chlorophyllin reduced the MMP-9 expression in vivo, and this effect was higher when it was coadministered with docetaxel. In coadministration, there was also a significant decrease in the total gelatinase activity in vivo. Finally, we found that only combined treatment reduced the micrometastatic lesions in the liver tissues. In conclusion, the coadministration of chlorophyllin and docetaxel may have a potential role in the control of metastatic processes by suppressing cell migration, invasion, and micrometastasis formation in triple-negative breast cancers.