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

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

Biomolecules (2020-09-04)
Prasanta Dey, Amit Kundu, Sang Hoon Han, Kyeong-Seok Kim, Jae Hyeon Park, Sungpil Yoon, In Su Kim, Hyung Sik Kim
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
α-Ketoglutaric acid, 99.0-101.0% (T)
Sigma-Aldrich
DL-Glyceraldehyde 3-phosphate solution, 45-55 mg/mL in H2O
Sigma-Aldrich
Pyruvic acid, 98%
Sigma-Aldrich
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Sigma-Aldrich
Goat serum
Supelco
Malic acid, Pharmaceutical Secondary Standard; Certified Reference Material