Anti-Neoplastic Role of the Triazole Analog TAN in Blocking Hedgehog Signaling Pathway Smoothened Receptors on the Human Colorectal Cancer Cell Line HCT116

Abstract

Seher A. Almedeny, Khalida K. Abbas Al-Kelaby, Hussein A. Abdul Hussein, Sarmad N. Gany, Najah Hadi.

Developing a new effective anticancer agent is a real hope and challenge, in this concern protein specific targeting provides very selective and promising approach, on the other hand cell culture model enables the researcher to make a rapid surveying of a wide number of investigational agents. Hedgehog receptors (SMO) are of the key bio-targets that may ensure more effective anticancer mode of treatment as sonic hedgehog (Shh) is expressed in many cancer types. In this study, a prior computerized model of editing and surveying drugs was done. a candidate antineoplastic drug TAN was obtained for an in vitro hedgehog SMO receptors blocking effect assessment on HCT116, a human colorectal cancer (CRC) cell line in comparison with Itraconazole (ITC), and the standard anticancer agents doxorubicin (DOX) and 5- fluorouracil (5 FU) the known SMO blocking agent, together with the cytotoxic effect assessment on the HCT 116 cells and Vero cells for the above mentioned drugs. This research was designed to survey and assign a candidate drug with high affinity to block SMO receptors of Hedgehog signaling pathway of HCT 116 colorectal cancer cells. The results revealed that TAN may give a promising role in therapeutic approach of colorectal cancer. It showed an in silico parameters as anticancer agent by Van der Waals interaction of TAN force field with a scaffold like minor groove at twisted region of smoothed receptor. This interaction between TAN and this region was referred to as reliable mechanism of impairment of cell proliferation or invasiveness (according to In silico model software reliability). Also TAN has a significant antineoplastic effect on colorectal cancer HCT116 cell line represented by its significant decreasing of the cellular viability. In addition, TAN displayed significant safety characteristics from the measured parameters on Vero cell line in this research. We concluded that the SMO blocking investigational agent TAN has a reasonable and significant antineoplastic effect on colorectal cancer HCT116 cells represented by its significant decreasing of the cellular viability and reduction of target binding energy. TAN also displayed significant safety characteristics from the measured parameters on Vero cell line in this research.