Girinimbine Inhibits the Proliferation, Migration, and Invasion of Human Breast Cancer Cells via Induction of Apoptosis, Suppression of Cell Migration and Invasion and Inhibition of MEK/ERK and STAT3 Signaling Pathways

Abstract

Background: The currently used anticancer drugs against breast cancer possess serious side effects, have limited efficacy, and often lead to recurrence of the malignancy. The main aim of the current research was to investigate the anticancer potential of girinimbine, a naturally occurring carbazole alkaloid, against estrogen receptor (ER)negative breast cancer cells (MDA-MB-453) along with its effects on cell migration and invasion, apoptosis, and the MEK/ERK/STAT3 pathway. Material/Methods: MTT assay was used to evaluate antiproliferative effects of girinimbine while as clonogenic assay was used to study cell colony formation. Transwell migration and invasion assays were performed to study the effects on cell migration and invasion. Fluorescence microscopy using acridine orange/ethidium bromide was used to study apoptotic effects of girinimbine, which was quantified by annexin V-FITC assay. Effects of girinimbine on the MEK/ERK and STAT3 signaling pathways were evaluated by western blot assay. Results: Results showed that girinimbine exhibited dose-dependent as well as time-dependent antiproliferative effects in MDA-MB-453 cells; in addition it strongly inhibited cell colony potency of these cancerous cells. Girinimbine could inhibit both cancer cell migration as well as invasion. Girinimbine induced potent chromatin condensation and nuclear fragmentation. The percentage of both early and late apoptotic cells increased significantly after girinimbine exposure. The anticancer effects of girinimbine were shown to be mediated via inhibition of the MEK/ERK as well as the STAT3 signaling pathways. Conclusions: In conclusion, it may be proposed that girinimbine could be a promising anticancer agent against breast cancer provided further in-depth studies are carried out.