Raptinal ameliorates 1,2-dimethylhydrazine-induced colon cancer through p53/Bcl2/Bax/caspase-3-mediated apoptotic events in vitro and in vivo.

OBJECTIVES: Colon carcinoma stands as the most familiar malignancy throughout across the globe. Raptinal induce apoptosis through the alteration of cellular events. Thus, in the present investigation, the anticancer activity of raptinal counter to 1,2-dimethylhydrazine (DMH) persuaded colon carcinoma has been evaluated through both in vivo and in vitro systems. MATERIALS AND METHODS: The pharmacophore analysis demonstrated the binding efficacy of raptinal with the apoptotic proteins. The chemotherapeutic activity of raptinal was examined through HT-29 human colorectal cancer (CRC) cell line as well as DMH persuaded CRC in the rat model. The cytotoxicity analysis, flow cytometry, and DAPI analysis have been carried out on HT-29 cell line through in vitro assessment. The colon carcinoma has been induced through DMH administration and subsequently Dextran sulfate sodium treatment in male Wistar rats. After 18 weeks of raptinal treatment, the colon tissues have been investigated for aberrant crypt foci (ACF) count, antioxidant status, histology, immunohistochemical assessment, and apoptotic analysis. RESULTS: The raptinal therapy on HT-29 cells demonstrated a substantial % of early apoptosis followed by G0 and G1 phase arrest, which subsequently led to apoptosis. Furthermore, it inhibits ACF development with improved colonic abrasions and structural integrity of colonic mucosa with increased levels of antioxidants, proapoptotic biomarkers including p53, caspase-3, Bax and downstream effects of Bcl-2, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 mutation. CONCLUSIONS: These findings indicate the raptinal effectively reduces colon cancer by inducing apoptosis through p53/Bcl2/Bax/caspase-3 pathway and suppressing IL-6, TNF-mediated chronic inflammation in the colon cancer microenvironment.

Decrypting a path based approach for identifying the interplay between PI3K and GSK3 signaling cascade from the perspective of cancer.

Cancer is one of those leading diseases worldwide, which takes millions of lives every year. Researchers are continuously looking for specific approaches to eradicate the deadly disease, ensuring minimal adverse effects along with more therapeutic significance. Targeting of different aberrantly regulated signaling pathways, involved in cancer, is surely one of the revolutionary chemotherapeutic approach. In this instance, GSK3 and PI3K signaling cascades are considered as important role player for both the oncogenic activation and inactivation which further leads to cancer proliferation and metastasis. In this review, we have discussed the potential role of GSK3 and PI3K signaling in cancer, and we further established the crosstalk between PI3K and GSK3 signaling, through showcasing their cross activation, cross inhibition and convergence pathways in association with cancer. We also exhibited the effect of GSK3 on the efficacy of PI3K inhibitors to overcome the drug resistance and preventing the cell proliferation, metastasis in a combinatorial way with GSK3 inhibitors for a better treatment strategy in clinical settings.