Biological Evaluation of Oxindole Derivative as a Novel Anticancer Agent against Human Kidney Carcinoma Cells

Abstract

Renal cell carcinoma has emerged as one of the leading causes of cancer-related deaths in the USA. Here, we examined the anticancer profile of oxindole derivatives (SH-859) in human renal cancer cells. Targeting 786-O cells by SH-859 inhibited cell growth and affected the protein kinase B/mechanistic target of rapamycin 1 pathway, which in turn downregulated the expression of glycolytic enzymes, including lactate dehydrogenase A and glucose transporter-1, as well as other signaling proteins. Treatment with SH-859 altered glycolysis, mitochondrial function, and levels of adenosine triphosphate and cellular metabolites. Flow cytometry revealed the induction of apoptosis and G0/G1 cell cycle arrest in renal cancer cells following SH-859 treatment. Induction of autophagy was also confirmed after SH-859 treatment by acridine orange and monodansylcadaverine staining, immunocytochemistry, and Western blot analyses. Finally, SH-859 also inhibited the tumor development in a xenograft model. Thus, SH-859 can serve as a potential molecule for the treatment of human renal carcinoma.

Design, Synthesis, and Evaluation of the COX-2 Inhibitory Activities of New 1,3-Dihydro-2H-indolin-2-one Derivatives

“…Oxindoles (such as 1,3-dihydro- 2H -indole-2-one) ( Figure 1 ), which are endogenous heteroaromatic organic compounds in animals and natural products of various plants [ 22 , 23 ], are the core structure of many biologically important compounds [ 24 , 25 ] and have been used to treat infections, cancer, arthritis, and other types of mild physical inflammation [ 26 , 27 , 28 ]. The role of oxindole as a chemical scaffold for fabricating and designing biological drug agents can be attributed to its ability to be modified by numerous chemical groups to generate novel biological functions.…”