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 this research was to investigate the anticancer potential of
Girinimbine, a naturally occurring
carbazole alkaloid, against ER-negative
breast cancer cells (MDA-MB-453) along with its effects on cell migration and invasion, apoptosis, and
MEK/ERK/STAT3 pathway. MTT assay was used to evaluate antiproliferative effects of
Girinimbine while a clonogenic assay was used to study cell colony formation. Transwell migration and invasion assays were involved to study its 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
MEK/ERK and STAT3 signalling pathways were evaluated by western blot assay. Results showed that
girinimbine exhibited dose-dependent as well as time-dependent antiproliferative effects in MDA-MB-453 cells along with strongly inhibiting the cell colony potency of these cancerous cells.
Girinimbine can inhibit both
cancer cell migration as well as invasion.
Girinimbine has 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 STAT3 signalling pathways. 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.