HuaChanSu suppresses the growth of hepatocellular carcinoma cells by interfering with pentose phosphate pathway through down-regulation of G6PD enzyme activity and expression
HuaChanSu is active water extracts from the skin of Bufo bufo gargarizans Cantor. It has been already used to treat clinical cancers including HCC (Hepatocellular carcinoma, HCC), however, the molecular mechanisms under HuaChanSu's anti-cancer effects remain unclear. PPP (Pentose phosphate path...
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| Format: | Article |
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Elsevier
2024-02-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024011757 |
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| author | Qi Wu Xue-li Ge Zi-kai Geng Hao Wu Jing-yi Yang Shi-rong Cao Ai-lin Yang |
| author_facet | Qi Wu Xue-li Ge Zi-kai Geng Hao Wu Jing-yi Yang Shi-rong Cao Ai-lin Yang |
| author_sort | Qi Wu |
| collection | DOAJ |
| description | HuaChanSu is active water extracts from the skin of Bufo bufo gargarizans Cantor. It has been already used to treat clinical cancers including HCC (Hepatocellular carcinoma, HCC), however, the molecular mechanisms under HuaChanSu's anti-cancer effects remain unclear. PPP (Pentose phosphate pathway, PPP), the major source of ribose and NADPH (Nicotinamide adenine dinucleotide phosphate, NADPH), is always over-activated and particularly critical for tumor cells growth. In this study, firstly, we illustrate that HuaChanSu restrains the growth of human hepatoma cells. More importantly, we demonstrate that the expression of G6PD (Glucose-6-phosphate dehydrogenase, G6PD), the first rate-limiting enzyme of the PPP, is restrained in human hepatoma cells after treatment with HuaChanSu. Additionally, our results show that G6PD enzyme activity and dimer formation are inhibited by HuaChanSu. Furthermore, we find that HuaChanSu could inhibit NADPH production and nucleotide level. In addition, we identify that expression of PLK1 (Polo-like kinase 1, PLK1) is also reduced in response to HuaChanSu, and knockdown of PLK1 restrains enzyme activity and dimer formation of G6PD, but has no effect on G6PD protein level. Subsequently, we demonstrate that inhibition of G6PD could restrain the proliferation of tumor cells and enhance the inhibitory effect of HuaChanSu on cell proliferation of human hepatoma cells. In conclusion, for the first time, our study reveals that HuaChanSu interferes with PPP via suppression of G6PD expression and enzyme activity to restrain growth of tumor cells, and these results provide a novel insight for the anti-hepatoma mechanisms of HuaChanSu and promote the innovation of the research model of TCM. Moreover, the development of drugs targeting abnormal tumor metabolism is currently a hot topic, our works provide theoretical support for further drug development from HuaChanSu, meanwhile, the revelation of the new molecular mechanism also provides a new perspective for the study of the pathogenesis of liver cancer. Short abstract: HuaChanSu suppresses expression of G6PD, the first rate-limiting enzyme of the PPP, restrains G6PD enzyme activity and dimer formation via inhibition of PLK1, knockdown of G6PD could impair the growth of human hepatoma cells and increase the blocking effect of HuaChanSu on cell proliferation of cancer cells. In addition, HuaChanSu restrains NADPH production and nucleotide level, implying the suppression of PPP flux. Our study suggests that HuaChanSu interferes with PPP via G6PD inhibition to exert anti-hepatoma effects. |
| first_indexed | 2024-03-08T00:11:08Z |
| format | Article |
| id | doaj.art-661ebda8e0ea49bd8abf5726163d4cde |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T00:11:08Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-661ebda8e0ea49bd8abf5726163d4cde2024-02-17T06:39:48ZengElsevierHeliyon2405-84402024-02-01103e25144HuaChanSu suppresses the growth of hepatocellular carcinoma cells by interfering with pentose phosphate pathway through down-regulation of G6PD enzyme activity and expressionQi Wu0Xue-li Ge1Zi-kai Geng2Hao Wu3Jing-yi Yang4Shi-rong Cao5Ai-lin Yang6School of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaSchool of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaSchool of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaSchool of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaSchool of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaSchool of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaCorresponding author. School of Pharmacy, Binzhou Medical University, 346 Guanhai Road, Laishan District, Yantai, Shandong, 264003, China.; School of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaHuaChanSu is active water extracts from the skin of Bufo bufo gargarizans Cantor. It has been already used to treat clinical cancers including HCC (Hepatocellular carcinoma, HCC), however, the molecular mechanisms under HuaChanSu's anti-cancer effects remain unclear. PPP (Pentose phosphate pathway, PPP), the major source of ribose and NADPH (Nicotinamide adenine dinucleotide phosphate, NADPH), is always over-activated and particularly critical for tumor cells growth. In this study, firstly, we illustrate that HuaChanSu restrains the growth of human hepatoma cells. More importantly, we demonstrate that the expression of G6PD (Glucose-6-phosphate dehydrogenase, G6PD), the first rate-limiting enzyme of the PPP, is restrained in human hepatoma cells after treatment with HuaChanSu. Additionally, our results show that G6PD enzyme activity and dimer formation are inhibited by HuaChanSu. Furthermore, we find that HuaChanSu could inhibit NADPH production and nucleotide level. In addition, we identify that expression of PLK1 (Polo-like kinase 1, PLK1) is also reduced in response to HuaChanSu, and knockdown of PLK1 restrains enzyme activity and dimer formation of G6PD, but has no effect on G6PD protein level. Subsequently, we demonstrate that inhibition of G6PD could restrain the proliferation of tumor cells and enhance the inhibitory effect of HuaChanSu on cell proliferation of human hepatoma cells. In conclusion, for the first time, our study reveals that HuaChanSu interferes with PPP via suppression of G6PD expression and enzyme activity to restrain growth of tumor cells, and these results provide a novel insight for the anti-hepatoma mechanisms of HuaChanSu and promote the innovation of the research model of TCM. Moreover, the development of drugs targeting abnormal tumor metabolism is currently a hot topic, our works provide theoretical support for further drug development from HuaChanSu, meanwhile, the revelation of the new molecular mechanism also provides a new perspective for the study of the pathogenesis of liver cancer. Short abstract: HuaChanSu suppresses expression of G6PD, the first rate-limiting enzyme of the PPP, restrains G6PD enzyme activity and dimer formation via inhibition of PLK1, knockdown of G6PD could impair the growth of human hepatoma cells and increase the blocking effect of HuaChanSu on cell proliferation of cancer cells. In addition, HuaChanSu restrains NADPH production and nucleotide level, implying the suppression of PPP flux. Our study suggests that HuaChanSu interferes with PPP via G6PD inhibition to exert anti-hepatoma effects.http://www.sciencedirect.com/science/article/pii/S2405844024011757HuaChanSuG6PDPLK1Pentose phosphate pathwayHepatocellular carcinoma |
| spellingShingle | Qi Wu Xue-li Ge Zi-kai Geng Hao Wu Jing-yi Yang Shi-rong Cao Ai-lin Yang HuaChanSu suppresses the growth of hepatocellular carcinoma cells by interfering with pentose phosphate pathway through down-regulation of G6PD enzyme activity and expression Heliyon HuaChanSu G6PD PLK1 Pentose phosphate pathway Hepatocellular carcinoma |
| title | HuaChanSu suppresses the growth of hepatocellular carcinoma cells by interfering with pentose phosphate pathway through down-regulation of G6PD enzyme activity and expression |
| title_full | HuaChanSu suppresses the growth of hepatocellular carcinoma cells by interfering with pentose phosphate pathway through down-regulation of G6PD enzyme activity and expression |
| title_fullStr | HuaChanSu suppresses the growth of hepatocellular carcinoma cells by interfering with pentose phosphate pathway through down-regulation of G6PD enzyme activity and expression |
| title_full_unstemmed | HuaChanSu suppresses the growth of hepatocellular carcinoma cells by interfering with pentose phosphate pathway through down-regulation of G6PD enzyme activity and expression |
| title_short | HuaChanSu suppresses the growth of hepatocellular carcinoma cells by interfering with pentose phosphate pathway through down-regulation of G6PD enzyme activity and expression |
| title_sort | huachansu suppresses the growth of hepatocellular carcinoma cells by interfering with pentose phosphate pathway through down regulation of g6pd enzyme activity and expression |
| topic | HuaChanSu G6PD PLK1 Pentose phosphate pathway Hepatocellular carcinoma |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024011757 |
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