Biological Evaluation of Oxindole Derivative as a Novel Anticancer Agent against Human Kidney Carcinoma Cells.
Prasanta DeyAmit KunduSang Hoon HanKyeong-Seok KimJae Hyeon ParkSungpil YoonIn Su KimHyung-Sik KimPublished in: Biomolecules (2020)
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.
Keyphrases
- cell cycle arrest
- cell death
- endothelial cells
- flow cytometry
- oxidative stress
- renal cell carcinoma
- protein kinase
- endoplasmic reticulum stress
- induced apoptosis
- adipose tissue
- poor prognosis
- pi k akt
- induced pluripotent stem cells
- blood pressure
- skeletal muscle
- cancer therapy
- long non coding rna
- metabolic syndrome
- combination therapy
- risk assessment
- insulin resistance
- glycemic control