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

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/mechanisti...

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Autores principales: Dey, Prasanta, Kundu, Amit, Han, Sang Hoon, Kim, Kyeong-Seok, Park, Jae Hyeon, Yoon, Sungpil, Kim, In Su, Kim, Hyung Sik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565513/
https://www.ncbi.nlm.nih.gov/pubmed/32878322
http://dx.doi.org/10.3390/biom10091260
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author Dey, Prasanta
Kundu, Amit
Han, Sang Hoon
Kim, Kyeong-Seok
Park, Jae Hyeon
Yoon, Sungpil
Kim, In Su
Kim, Hyung Sik
author_facet Dey, Prasanta
Kundu, Amit
Han, Sang Hoon
Kim, Kyeong-Seok
Park, Jae Hyeon
Yoon, Sungpil
Kim, In Su
Kim, Hyung Sik
author_sort Dey, Prasanta
collection PubMed
description 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.
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spelling pubmed-75655132020-10-26 Biological Evaluation of Oxindole Derivative as a Novel Anticancer Agent against Human Kidney Carcinoma Cells Dey, Prasanta Kundu, Amit Han, Sang Hoon Kim, Kyeong-Seok Park, Jae Hyeon Yoon, Sungpil Kim, In Su Kim, Hyung Sik Biomolecules Article 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. MDPI 2020-08-31 /pmc/articles/PMC7565513/ /pubmed/32878322 http://dx.doi.org/10.3390/biom10091260 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dey, Prasanta
Kundu, Amit
Han, Sang Hoon
Kim, Kyeong-Seok
Park, Jae Hyeon
Yoon, Sungpil
Kim, In Su
Kim, Hyung Sik
Biological Evaluation of Oxindole Derivative as a Novel Anticancer Agent against Human Kidney Carcinoma Cells
title Biological Evaluation of Oxindole Derivative as a Novel Anticancer Agent against Human Kidney Carcinoma Cells
title_full Biological Evaluation of Oxindole Derivative as a Novel Anticancer Agent against Human Kidney Carcinoma Cells
title_fullStr Biological Evaluation of Oxindole Derivative as a Novel Anticancer Agent against Human Kidney Carcinoma Cells
title_full_unstemmed Biological Evaluation of Oxindole Derivative as a Novel Anticancer Agent against Human Kidney Carcinoma Cells
title_short Biological Evaluation of Oxindole Derivative as a Novel Anticancer Agent against Human Kidney Carcinoma Cells
title_sort biological evaluation of oxindole derivative as a novel anticancer agent against human kidney carcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565513/
https://www.ncbi.nlm.nih.gov/pubmed/32878322
http://dx.doi.org/10.3390/biom10091260
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