Cryptolepine suppresses breast adenocarcinoma via inhibition of HIF-1 mediated glycolysis
As a characteristic transcription factor in solid tumors, hypoxia inducible factor-1 (HIF-1) acts as a master regulator in breast cancer progression. Cryptolepine, as a natural alkaloid, noticeably inhibited HIF-1 transcriptional activity and decreased the protein expression of hypoxia-induced HIF-1...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-09-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222007089 |
| _version_ | 1811338209340162048 |
|---|---|
| author | Zhiyuan Zheng Ting Xu Zhiyan Liu Wenyue Tian Zhi-Hong Jiang Guo-Yuan Zhu Ting Li Jin Gao Li-Ping Bai |
| author_facet | Zhiyuan Zheng Ting Xu Zhiyan Liu Wenyue Tian Zhi-Hong Jiang Guo-Yuan Zhu Ting Li Jin Gao Li-Ping Bai |
| author_sort | Zhiyuan Zheng |
| collection | DOAJ |
| description | As a characteristic transcription factor in solid tumors, hypoxia inducible factor-1 (HIF-1) acts as a master regulator in breast cancer progression. Cryptolepine, as a natural alkaloid, noticeably inhibited HIF-1 transcriptional activity and decreased the protein expression of hypoxia-induced HIF-1α in breast cancer cells. Further study showed that cryptolepine blocked HIF-1-mediated glycolysis and suppressed the expression of multiple glycolysis enzymes, resulting in a decrease in ATP production in hypoxic T47D and 4T1 cells. Meanwhile, cryptolepine displayed potent suppressive effect on tumor growth in a dose-dependent manner. In 4T1 tumor xenografts, cryptolepine reduced HIF-1α protein expression, and thus decreased the levels of both lactate acid and ATP productions. The mechanistic study revealed that cryptolepine could effectively suppress the process of HIF-1α mRNA translation rather than transcription, which was attributed to the inhibition on the phosphorylation of eIF4E regulated by both MAPK and mTOR signaling pathways. Collectively, current findings suggested that cryptolepine possesses the potential to treat breast cancers by modulating HIF-1 both in vitro and in vivo. |
| first_indexed | 2024-04-13T18:06:41Z |
| format | Article |
| id | doaj.art-887a57e326124b0e89e981000b540321 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-13T18:06:41Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-887a57e326124b0e89e981000b5403212022-12-22T02:36:03ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-09-01153113319Cryptolepine suppresses breast adenocarcinoma via inhibition of HIF-1 mediated glycolysisZhiyuan Zheng0Ting Xu1Zhiyan Liu2Wenyue Tian3Zhi-Hong Jiang4Guo-Yuan Zhu5Ting Li6Jin Gao7Li-Ping Bai8State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, 999078, Macau, People's Republic of ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, 999078, Macau, People's Republic of ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, 999078, Macau, People's Republic of ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, 999078, Macau, People's Republic of ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, 999078, Macau, People's Republic of China; Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease (Macau University of Science and Technology), 999078, Macau, People's Republic of ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, 999078, Macau, People's Republic of China; Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease (Macau University of Science and Technology), 999078, Macau, People's Republic of ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, 999078, Macau, People's Republic of ChinaIncreasePharm (Hengqin) Institute Co., Ltd, Zhu Hai, Guangdong 519031, People’s Republic of ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, 999078, Macau, People's Republic of China; Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease (Macau University of Science and Technology), 999078, Macau, People's Republic of China; Corresponding author at: State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, 999078, Macau, People's Republic of China.As a characteristic transcription factor in solid tumors, hypoxia inducible factor-1 (HIF-1) acts as a master regulator in breast cancer progression. Cryptolepine, as a natural alkaloid, noticeably inhibited HIF-1 transcriptional activity and decreased the protein expression of hypoxia-induced HIF-1α in breast cancer cells. Further study showed that cryptolepine blocked HIF-1-mediated glycolysis and suppressed the expression of multiple glycolysis enzymes, resulting in a decrease in ATP production in hypoxic T47D and 4T1 cells. Meanwhile, cryptolepine displayed potent suppressive effect on tumor growth in a dose-dependent manner. In 4T1 tumor xenografts, cryptolepine reduced HIF-1α protein expression, and thus decreased the levels of both lactate acid and ATP productions. The mechanistic study revealed that cryptolepine could effectively suppress the process of HIF-1α mRNA translation rather than transcription, which was attributed to the inhibition on the phosphorylation of eIF4E regulated by both MAPK and mTOR signaling pathways. Collectively, current findings suggested that cryptolepine possesses the potential to treat breast cancers by modulating HIF-1 both in vitro and in vivo.http://www.sciencedirect.com/science/article/pii/S0753332222007089Cryptolepine (CLP)Hypoxia inducible factor-1 (HIF-1)GlycolysisBreast cancer |
| spellingShingle | Zhiyuan Zheng Ting Xu Zhiyan Liu Wenyue Tian Zhi-Hong Jiang Guo-Yuan Zhu Ting Li Jin Gao Li-Ping Bai Cryptolepine suppresses breast adenocarcinoma via inhibition of HIF-1 mediated glycolysis Biomedicine & Pharmacotherapy Cryptolepine (CLP) Hypoxia inducible factor-1 (HIF-1) Glycolysis Breast cancer |
| title | Cryptolepine suppresses breast adenocarcinoma via inhibition of HIF-1 mediated glycolysis |
| title_full | Cryptolepine suppresses breast adenocarcinoma via inhibition of HIF-1 mediated glycolysis |
| title_fullStr | Cryptolepine suppresses breast adenocarcinoma via inhibition of HIF-1 mediated glycolysis |
| title_full_unstemmed | Cryptolepine suppresses breast adenocarcinoma via inhibition of HIF-1 mediated glycolysis |
| title_short | Cryptolepine suppresses breast adenocarcinoma via inhibition of HIF-1 mediated glycolysis |
| title_sort | cryptolepine suppresses breast adenocarcinoma via inhibition of hif 1 mediated glycolysis |
| topic | Cryptolepine (CLP) Hypoxia inducible factor-1 (HIF-1) Glycolysis Breast cancer |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222007089 |
| work_keys_str_mv | AT zhiyuanzheng cryptolepinesuppressesbreastadenocarcinomaviainhibitionofhif1mediatedglycolysis AT tingxu cryptolepinesuppressesbreastadenocarcinomaviainhibitionofhif1mediatedglycolysis AT zhiyanliu cryptolepinesuppressesbreastadenocarcinomaviainhibitionofhif1mediatedglycolysis AT wenyuetian cryptolepinesuppressesbreastadenocarcinomaviainhibitionofhif1mediatedglycolysis AT zhihongjiang cryptolepinesuppressesbreastadenocarcinomaviainhibitionofhif1mediatedglycolysis AT guoyuanzhu cryptolepinesuppressesbreastadenocarcinomaviainhibitionofhif1mediatedglycolysis AT tingli cryptolepinesuppressesbreastadenocarcinomaviainhibitionofhif1mediatedglycolysis AT jingao cryptolepinesuppressesbreastadenocarcinomaviainhibitionofhif1mediatedglycolysis AT lipingbai cryptolepinesuppressesbreastadenocarcinomaviainhibitionofhif1mediatedglycolysis |