Unveiling the chemical profile, anti-proliferative, pro-apoptotic and anti-migratory effect of Indigofera linifolia in liver and breast cancer cells

Abstract

Chemotherapeutic medications have a crucial role in treating various types of cancer. Nevertheless, the emergence of resistance in cancer cells and the detrimental effects on healthy cells emphasize the necessity for tailored therapies that selectively eradicate cancer cells. Indigofera linifolia has been extensively utilized for the management of several medical conditions, such as inflammation, cancer and febrile eruptions. This study's primary goal is to clarify the molecular mechanism of action of the methanol extract from Indigofera linifolia (ILM) and investigate any potential anticancer effects. Initially, we conducted MTT and flow cytometry analyses to evaluate cellular proliferation, apoptosis, and cell cycle arrest. Subsequently, we examined cell metastasis and protein markers using transwell migration, matrigel invasion assays, and western blotting techniques. The use of ILM led to a significant decrease in cell growth, an upsurge in programmed cell death, and a prevention of the spread of cancer cells in HCCLM3 and MDA-MB-231 cell lines. The molecular mechanism underlying the observed effects of ILM involves an increase in the levels of cleaved-PARP, cleaved-caspases (−3/-7/-8/-9), and proapoptotic proteins (Bax, Bak, and Bid), while decreased the level of protein that help cells divide (Cyclin D1/E), stop cells from dying (Bcl-xL, Bcl-2, XIAP, and Survivin), and proteins that help cells spread (MMP-2/-9). In addition, ILM affect the JAK/STAT3 signaling pathway in MDA-MB-231 cells, while triggers the JNK/MAPK pathway in HCCLM3 cells. Our study has provided additional evidence supporting the effectiveness of inhibiting STAT3 using the stattic inhibitor and JNK using the JNK inhibitor in reversing apoptosis induced by ILM in breast and liver cancer cells, respectively. Overall, our findings indicate that ILM possesses potential anticancer properties through modulation of several signaling pathways and found it a viable therapeutic option for cancer interventions.