Visnagin inhibits cervical cancer cells proliferation through the induction of apoptosis and modulation of PI3K/AKT/mTOR and MAPK signaling pathway

Cervical cancer, a silent killer is a second most common type of malignant tumor detected in women’s world wide. In modern medicine the usage of phytochemicals to develop drugs for treating various chronic diseases is rapidly increasing. One such phytochemical is visnagin, a furanochrome present in fruits of Ammi visnaga. We investigated the anticarcinogenic potency of visnagin against human cervical carcinoma cells. The antioxidant potency of visnagin was analyzed with FRAP assay, DPPH assay, Chemiluminscence assay and ORAC assay. The cytotoxic effect of visnagin on normal epithelial Vero cells and human cervical cancer HeLa cells were analyzed using MTT assay. The effect of visnagin on antioxidant system was examined by measuring the levels of TBARS, SOD and GSH using the colorimetric assay techniques. DCFH-DA staining, AO/EtBr staining, propidium iodide staining was performed to assess the apoptotic induction potency of visnagin against cervical cancer cells. The ability of visnagin to inhibit cancer cell migration was examined with scratch wound assay. The anticarcinogenic property of visnagin was confirmed by analyzing the gene expression of PI3K/AKT/mTOR signaling proteins and MAPK signaling proteins using qPCR analysis. Visnagin exhibited increased Trolox equivalent value in all the four antioxidant potency estimating experiments. Visnagin induced cytotoxic effect only on carcinoma cells, decreased the antioxidants and increased the generation of ROS. It also induced apoptosis and inhibited the cancer cell migration. The qPCR analysis confirms visnagin decreases the gene expression cell cycle regulating protein of both PI3K/AKT/mTOR and MAPK pathway. Overall our results authentically prove visnagin inhibits the progression of cervical cancer in vitro. Therefore it can be an ideal drug of choice which can subject to further investigation for treating cervical cancer.