Cyanidin Curtails Renal Cell Carcinoma Tumorigenesis

Background/Aims: Cyanidin is an anthocyanin found in many foods. Although its variable antioxidant levels are well-documented, little is known about its effects on renal cell carcinoma (RCC) tumorigenesis. This study, therefore, investigated the effects of cyanidin on the proliferation, migration, a...

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Main Authors: Xiaobing Liu, Dangling Zhang, Yaxing Hao, Qian Liu, Yuqi Wu, Xin Liu, Jing Luo, Tao Zhou, Bishao Sun, Xing Luo, Jie Xu, Qingqing Wang, Zhenxing Yang, Longkun Li
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2018-05-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:https://www.karger.com/Article/FullText/489658
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author Xiaobing Liu
Dangling Zhang
Yaxing Hao
Qian Liu
Yuqi Wu
Xin Liu
Jing Luo
Tao Zhou
Bishao Sun
Xing Luo
Jie Xu
Qingqing Wang
Zhenxing Yang
Longkun Li
author_facet Xiaobing Liu
Dangling Zhang
Yaxing Hao
Qian Liu
Yuqi Wu
Xin Liu
Jing Luo
Tao Zhou
Bishao Sun
Xing Luo
Jie Xu
Qingqing Wang
Zhenxing Yang
Longkun Li
author_sort Xiaobing Liu
collection DOAJ
description Background/Aims: Cyanidin is an anthocyanin found in many foods. Although its variable antioxidant levels are well-documented, little is known about its effects on renal cell carcinoma (RCC) tumorigenesis. This study, therefore, investigated the effects of cyanidin on the proliferation, migration, and invasion of renal cell carcinoma lines and demonstrated, for the first time, significant inhibitory effects of cyanidin on RCC tumorigenesis. Methods: RCC cells were treated with different doses of cyanidin and the effects were tested by Cell Counting Kit-8 reagent, clone formation assay, transwell assay, and flow cytometry. Moreover, the cyanidin-mediated mechanism that curtailed tumorigenesis was analyzed by RNA sequencing (RNA-seq). Sequencing data from The Cancer Genome Atlas (TCGA) were used to compare the expression of both early growth response protein 1 (EGR1) and selenoprotein W (SEPW1) in RCC and tumor-free adjacent normal tissue samples. Real-time PCR (RT-PCR) and/or western blot were used to assess the expression of E-cadherin, cleaved-caspase3, Bcl2, p62, and ATG4. Results: We found significantly greater induction of cell-cycle arrest, apoptosis, and suppression of RCC cell invasion and migration at concentrations of 25 µM and 100 µM than at a concentration of 50 µM. It was also discovered, first through RNA-seq then confirmed by RT-PCR, that cyanidin (100 µM) inhibited RCC carcinogenesis through EGR1 and SEPW1. TCGA data indicated that the expression level of EGR1 was lower and that of SEPW1 was higher in RCC tumor tissue than in normal tissues. Moreover, western blot and/or RT-PCR indicated that cleaved-caspase3 was enhanced and E-cadherin was inhibited by cyanidin treatment. Furthermore, western blot and RT-PCR also showed regulation of p62 and ATG4, which are associated with autophagy. Cyanidin in vivo significantly inhibited the growth of xenografts in nude mice. Conclusions: The results of this study showed the therapeutic potential of cyanidin for the treatment of RCC and the prevention of recurrence and metastasis.
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spelling doaj.art-4af89624019f47b8affd546a6d8f732d2022-12-22T01:14:25ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-05-014662517253110.1159/000489658489658Cyanidin Curtails Renal Cell Carcinoma TumorigenesisXiaobing LiuDangling ZhangYaxing HaoQian LiuYuqi WuXin LiuJing LuoTao ZhouBishao SunXing LuoJie XuQingqing WangZhenxing YangLongkun LiBackground/Aims: Cyanidin is an anthocyanin found in many foods. Although its variable antioxidant levels are well-documented, little is known about its effects on renal cell carcinoma (RCC) tumorigenesis. This study, therefore, investigated the effects of cyanidin on the proliferation, migration, and invasion of renal cell carcinoma lines and demonstrated, for the first time, significant inhibitory effects of cyanidin on RCC tumorigenesis. Methods: RCC cells were treated with different doses of cyanidin and the effects were tested by Cell Counting Kit-8 reagent, clone formation assay, transwell assay, and flow cytometry. Moreover, the cyanidin-mediated mechanism that curtailed tumorigenesis was analyzed by RNA sequencing (RNA-seq). Sequencing data from The Cancer Genome Atlas (TCGA) were used to compare the expression of both early growth response protein 1 (EGR1) and selenoprotein W (SEPW1) in RCC and tumor-free adjacent normal tissue samples. Real-time PCR (RT-PCR) and/or western blot were used to assess the expression of E-cadherin, cleaved-caspase3, Bcl2, p62, and ATG4. Results: We found significantly greater induction of cell-cycle arrest, apoptosis, and suppression of RCC cell invasion and migration at concentrations of 25 µM and 100 µM than at a concentration of 50 µM. It was also discovered, first through RNA-seq then confirmed by RT-PCR, that cyanidin (100 µM) inhibited RCC carcinogenesis through EGR1 and SEPW1. TCGA data indicated that the expression level of EGR1 was lower and that of SEPW1 was higher in RCC tumor tissue than in normal tissues. Moreover, western blot and/or RT-PCR indicated that cleaved-caspase3 was enhanced and E-cadherin was inhibited by cyanidin treatment. Furthermore, western blot and RT-PCR also showed regulation of p62 and ATG4, which are associated with autophagy. Cyanidin in vivo significantly inhibited the growth of xenografts in nude mice. Conclusions: The results of this study showed the therapeutic potential of cyanidin for the treatment of RCC and the prevention of recurrence and metastasis.https://www.karger.com/Article/FullText/489658Renal cell carcinomaCyanidinApoptosisMigrationInvasion
spellingShingle Xiaobing Liu
Dangling Zhang
Yaxing Hao
Qian Liu
Yuqi Wu
Xin Liu
Jing Luo
Tao Zhou
Bishao Sun
Xing Luo
Jie Xu
Qingqing Wang
Zhenxing Yang
Longkun Li
Cyanidin Curtails Renal Cell Carcinoma Tumorigenesis
Cellular Physiology and Biochemistry
Renal cell carcinoma
Cyanidin
Apoptosis
Migration
Invasion
title Cyanidin Curtails Renal Cell Carcinoma Tumorigenesis
title_full Cyanidin Curtails Renal Cell Carcinoma Tumorigenesis
title_fullStr Cyanidin Curtails Renal Cell Carcinoma Tumorigenesis
title_full_unstemmed Cyanidin Curtails Renal Cell Carcinoma Tumorigenesis
title_short Cyanidin Curtails Renal Cell Carcinoma Tumorigenesis
title_sort cyanidin curtails renal cell carcinoma tumorigenesis
topic Renal cell carcinoma
Cyanidin
Apoptosis
Migration
Invasion
url https://www.karger.com/Article/FullText/489658
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