Panduratin A Derivative Protects against Cisplatin-Induced Apoptosis of Renal Proximal Tubular Cells and Kidney Injury in Mice

Background: Panduratin A is a bioactive cyclohexanyl chalcone exhibiting several pharmacological activities, such as anti-inflammatory, anti-oxidative, and anti-cancer activities. Recently, the nephroprotective effect of panduratin A in cisplatin (CDDP) treatment was revealed. The present study exam...

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Autores principales:	Penjai Thongnuanjan, Sirima Soodvilai, Somsak Fongsupa, Natechanok Thipboonchoo, Napason Chabang, Bamroong Munyoo, Patoomratana Tuchinda, Sunhapas Soodvilai
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	apoptosis chemotherapy cyclohexanyl chalcone kidney oxidative stress Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/a234aad0aa5a4b31b478d65fab31b46e
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spelling	oai:doaj.org-article:a234aad0aa5a4b31b478d65fab31b46e2021-11-11T18:36:36ZPanduratin A Derivative Protects against Cisplatin-Induced Apoptosis of Renal Proximal Tubular Cells and Kidney Injury in Mice10.3390/molecules262166421420-3049https://doaj.org/article/a234aad0aa5a4b31b478d65fab31b46e2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6642https://doaj.org/toc/1420-3049Background: Panduratin A is a bioactive cyclohexanyl chalcone exhibiting several pharmacological activities, such as anti-inflammatory, anti-oxidative, and anti-cancer activities. Recently, the nephroprotective effect of panduratin A in cisplatin (CDDP) treatment was revealed. The present study examined the potential of certain compounds derived from panduratin A to protect against CDDP-induced nephrotoxicity. Methods: Three derivatives of panduratin A (DD-217, DD-218, and DD-219) were semi-synthesized from panduratin A. We investigated the effects and corresponding mechanisms of the derivatives of panduratin A for preventing nephrotoxicity of CDDP in both immortalized human renal proximal tubular cells (RPTEC/TERT1 cells) and mice. Results: Treating the cell with 10 µM panduratin A significantly reduced the viability of RPTEC/TERT1 cells compared to control (panduratin A: 72% ± 4.85%). Interestingly, DD-217, DD-218, and DD-219 at the same concentration did not significantly affect cell viability (92% ± 8.44%, 90% ± 7.50%, and 87 ± 5.2%, respectively). Among those derivatives, DD-218 exhibited the most protective effect against CDDP-induced renal proximal tubular cell apoptosis (control: 57% ± 1.23%; DD-218: 19% ± 10.14%; DD-219: 33% ± 14.06%). The cytoprotective effect of DD-218 was mediated via decreases in CDDP-induced mitochondria dysfunction, intracellular reactive oxygen species (ROS) generation, activation of ERK1/2, and cleaved-caspase 3 and 7. In addition, DD-218 attenuated CDDP-induced nephrotoxicity by a decrease in renal injury and improved in renal dysfunction in C57BL/6 mice. Importantly, DD-218 did not attenuate the anti-cancer efficacy of CDDP in non-small-cell lung cancer cells or colon cancer cells. Conclusions: This finding suggests that DD-218, a derivative of panduratin A, holds promise as an adjuvant therapy in patients receiving CDDP.Penjai ThongnuanjanSirima SoodvilaiSomsak FongsupaNatechanok ThipboonchooNapason ChabangBamroong MunyooPatoomratana TuchindaSunhapas SoodvilaiMDPI AGarticleapoptosischemotherapycyclohexanyl chalconekidneyoxidative stressOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6642, p 6642 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	apoptosis chemotherapy cyclohexanyl chalcone kidney oxidative stress Organic chemistry QD241-441
spellingShingle	apoptosis chemotherapy cyclohexanyl chalcone kidney oxidative stress Organic chemistry QD241-441 Penjai Thongnuanjan Sirima Soodvilai Somsak Fongsupa Natechanok Thipboonchoo Napason Chabang Bamroong Munyoo Patoomratana Tuchinda Sunhapas Soodvilai Panduratin A Derivative Protects against Cisplatin-Induced Apoptosis of Renal Proximal Tubular Cells and Kidney Injury in Mice
description	Background: Panduratin A is a bioactive cyclohexanyl chalcone exhibiting several pharmacological activities, such as anti-inflammatory, anti-oxidative, and anti-cancer activities. Recently, the nephroprotective effect of panduratin A in cisplatin (CDDP) treatment was revealed. The present study examined the potential of certain compounds derived from panduratin A to protect against CDDP-induced nephrotoxicity. Methods: Three derivatives of panduratin A (DD-217, DD-218, and DD-219) were semi-synthesized from panduratin A. We investigated the effects and corresponding mechanisms of the derivatives of panduratin A for preventing nephrotoxicity of CDDP in both immortalized human renal proximal tubular cells (RPTEC/TERT1 cells) and mice. Results: Treating the cell with 10 µM panduratin A significantly reduced the viability of RPTEC/TERT1 cells compared to control (panduratin A: 72% ± 4.85%). Interestingly, DD-217, DD-218, and DD-219 at the same concentration did not significantly affect cell viability (92% ± 8.44%, 90% ± 7.50%, and 87 ± 5.2%, respectively). Among those derivatives, DD-218 exhibited the most protective effect against CDDP-induced renal proximal tubular cell apoptosis (control: 57% ± 1.23%; DD-218: 19% ± 10.14%; DD-219: 33% ± 14.06%). The cytoprotective effect of DD-218 was mediated via decreases in CDDP-induced mitochondria dysfunction, intracellular reactive oxygen species (ROS) generation, activation of ERK1/2, and cleaved-caspase 3 and 7. In addition, DD-218 attenuated CDDP-induced nephrotoxicity by a decrease in renal injury and improved in renal dysfunction in C57BL/6 mice. Importantly, DD-218 did not attenuate the anti-cancer efficacy of CDDP in non-small-cell lung cancer cells or colon cancer cells. Conclusions: This finding suggests that DD-218, a derivative of panduratin A, holds promise as an adjuvant therapy in patients receiving CDDP.
format	article
author	Penjai Thongnuanjan Sirima Soodvilai Somsak Fongsupa Natechanok Thipboonchoo Napason Chabang Bamroong Munyoo Patoomratana Tuchinda Sunhapas Soodvilai
author_facet	Penjai Thongnuanjan Sirima Soodvilai Somsak Fongsupa Natechanok Thipboonchoo Napason Chabang Bamroong Munyoo Patoomratana Tuchinda Sunhapas Soodvilai
author_sort	Penjai Thongnuanjan
title	Panduratin A Derivative Protects against Cisplatin-Induced Apoptosis of Renal Proximal Tubular Cells and Kidney Injury in Mice
title_short	Panduratin A Derivative Protects against Cisplatin-Induced Apoptosis of Renal Proximal Tubular Cells and Kidney Injury in Mice
title_full	Panduratin A Derivative Protects against Cisplatin-Induced Apoptosis of Renal Proximal Tubular Cells and Kidney Injury in Mice
title_fullStr	Panduratin A Derivative Protects against Cisplatin-Induced Apoptosis of Renal Proximal Tubular Cells and Kidney Injury in Mice
title_full_unstemmed	Panduratin A Derivative Protects against Cisplatin-Induced Apoptosis of Renal Proximal Tubular Cells and Kidney Injury in Mice
title_sort	panduratin a derivative protects against cisplatin-induced apoptosis of renal proximal tubular cells and kidney injury in mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a234aad0aa5a4b31b478d65fab31b46e
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Panduratin A Derivative Protects against Cisplatin-Induced Apoptosis of Renal Proximal Tubular Cells and Kidney Injury in Mice

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