Carnosine Inhibits the Proliferation of Human Cervical Gland Carcinoma Cells Through Inhibiting Both Mitochondrial Bioenergetics and Glycolysis Pathways and Retarding Cell Cycle Progression

Carnosine has been demonstrated to play an antitumorigenic role in certain types of cancer. However, its underlying mechanism is unclear. In this study, the roles of carnosine in cell proliferation and its underlying mechanism were investigated in the cultured human cervical gland carcinoma cells He...

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Main Authors: Yun Bao MS, Saidan Ding PhD, Jiaoyan Cheng BS, Yuan Liu BS, Bingyu Wang BS, Huijuan Xu BS, Yao Shen PhD, Jianxin Lyu PhD
Format: Article
Language:English
Published: SAGE Publishing 2018-03-01
Series:Integrative Cancer Therapies
Online Access:https://doi.org/10.1177/1534735416684551
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author Yun Bao MS
Saidan Ding PhD
Jiaoyan Cheng BS
Yuan Liu BS
Bingyu Wang BS
Huijuan Xu BS
Yao Shen PhD
Jianxin Lyu PhD
author_facet Yun Bao MS
Saidan Ding PhD
Jiaoyan Cheng BS
Yuan Liu BS
Bingyu Wang BS
Huijuan Xu BS
Yao Shen PhD
Jianxin Lyu PhD
author_sort Yun Bao MS
collection DOAJ
description Carnosine has been demonstrated to play an antitumorigenic role in certain types of cancer. However, its underlying mechanism is unclear. In this study, the roles of carnosine in cell proliferation and its underlying mechanism were investigated in the cultured human cervical gland carcinoma cells HeLa and cervical squamous carcinoma cells SiHa. The results showed that carnosine exerted a significant inhibitory effect on the proliferation of HeLa cells, whereas its inhibitory action on the proliferation of SiHa cells was much weaker. Carnosine decreased the ATP content through inhibiting both mitochondrial respiration and glycolysis pathways in cultured HeLa cells but not SiHa cells. Carnosine reduced the activities of isocitrate dehydrogenase and malate dehydrogenase in TCA (tricarboxylic acid) cycle and the activities of mitochondrial electron transport chain complex I, II, III, and IV in HeLa cells but not SiHa cells. Carnosine also decreased the mRNA and protein expression levels of ClpP, which plays a key role in maintaining the mitochondrial function in HeLa cells. In addition, carnosine induced G1 arrest by inhibiting the G1-S phase transition in both HeLa and SiHa cells. Taken together, these findings suggest that carnosine has a strong inhibitory action on the proliferation of human cervical gland carcinoma cells rather than cervical squamous carcinoma cells. Mitochondrial bioenergetics and glycolysis pathways and cell cycle may be involved in the carnosine action on the cell proliferation in cultured human cervical gland carcinoma cells HeLa.
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spelling doaj.art-7998a0d9081c4c31a829a1d5fffc91a52022-12-21T22:37:55ZengSAGE PublishingIntegrative Cancer Therapies1534-73541552-695X2018-03-011710.1177/1534735416684551Carnosine Inhibits the Proliferation of Human Cervical Gland Carcinoma Cells Through Inhibiting Both Mitochondrial Bioenergetics and Glycolysis Pathways and Retarding Cell Cycle ProgressionYun Bao MS0Saidan Ding PhD1Jiaoyan Cheng BS2Yuan Liu BS3Bingyu Wang BS4Huijuan Xu BS5Yao Shen PhD6Jianxin Lyu PhD7Jinhua People’s Hospital, Jinhua, Zhejiang, Peoples Republic of ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, Peoples Republic of ChinaWenzhou Medical University, Wenzhou, Zhejiang, Peoples Republic of ChinaWenzhou Medical University, Wenzhou, Zhejiang, Peoples Republic of ChinaWenzhou Medical University, Wenzhou, Zhejiang, Peoples Republic of ChinaWenzhou Medical University, Wenzhou, Zhejiang, Peoples Republic of ChinaWenzhou Medical University, Wenzhou, Zhejiang, Peoples Republic of ChinaWenzhou Medical University, Wenzhou, Zhejiang, Peoples Republic of ChinaCarnosine has been demonstrated to play an antitumorigenic role in certain types of cancer. However, its underlying mechanism is unclear. In this study, the roles of carnosine in cell proliferation and its underlying mechanism were investigated in the cultured human cervical gland carcinoma cells HeLa and cervical squamous carcinoma cells SiHa. The results showed that carnosine exerted a significant inhibitory effect on the proliferation of HeLa cells, whereas its inhibitory action on the proliferation of SiHa cells was much weaker. Carnosine decreased the ATP content through inhibiting both mitochondrial respiration and glycolysis pathways in cultured HeLa cells but not SiHa cells. Carnosine reduced the activities of isocitrate dehydrogenase and malate dehydrogenase in TCA (tricarboxylic acid) cycle and the activities of mitochondrial electron transport chain complex I, II, III, and IV in HeLa cells but not SiHa cells. Carnosine also decreased the mRNA and protein expression levels of ClpP, which plays a key role in maintaining the mitochondrial function in HeLa cells. In addition, carnosine induced G1 arrest by inhibiting the G1-S phase transition in both HeLa and SiHa cells. Taken together, these findings suggest that carnosine has a strong inhibitory action on the proliferation of human cervical gland carcinoma cells rather than cervical squamous carcinoma cells. Mitochondrial bioenergetics and glycolysis pathways and cell cycle may be involved in the carnosine action on the cell proliferation in cultured human cervical gland carcinoma cells HeLa.https://doi.org/10.1177/1534735416684551
spellingShingle Yun Bao MS
Saidan Ding PhD
Jiaoyan Cheng BS
Yuan Liu BS
Bingyu Wang BS
Huijuan Xu BS
Yao Shen PhD
Jianxin Lyu PhD
Carnosine Inhibits the Proliferation of Human Cervical Gland Carcinoma Cells Through Inhibiting Both Mitochondrial Bioenergetics and Glycolysis Pathways and Retarding Cell Cycle Progression
Integrative Cancer Therapies
title Carnosine Inhibits the Proliferation of Human Cervical Gland Carcinoma Cells Through Inhibiting Both Mitochondrial Bioenergetics and Glycolysis Pathways and Retarding Cell Cycle Progression
title_full Carnosine Inhibits the Proliferation of Human Cervical Gland Carcinoma Cells Through Inhibiting Both Mitochondrial Bioenergetics and Glycolysis Pathways and Retarding Cell Cycle Progression
title_fullStr Carnosine Inhibits the Proliferation of Human Cervical Gland Carcinoma Cells Through Inhibiting Both Mitochondrial Bioenergetics and Glycolysis Pathways and Retarding Cell Cycle Progression
title_full_unstemmed Carnosine Inhibits the Proliferation of Human Cervical Gland Carcinoma Cells Through Inhibiting Both Mitochondrial Bioenergetics and Glycolysis Pathways and Retarding Cell Cycle Progression
title_short Carnosine Inhibits the Proliferation of Human Cervical Gland Carcinoma Cells Through Inhibiting Both Mitochondrial Bioenergetics and Glycolysis Pathways and Retarding Cell Cycle Progression
title_sort carnosine inhibits the proliferation of human cervical gland carcinoma cells through inhibiting both mitochondrial bioenergetics and glycolysis pathways and retarding cell cycle progression
url https://doi.org/10.1177/1534735416684551
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