2. Academic Validation
  3. Cryptolepine suppresses breast adenocarcinoma via inhibition of HIF-1 mediated glycolysis

Cryptolepine suppresses breast adenocarcinoma via inhibition of HIF-1 mediated glycolysis

  • Biomed Pharmacother. 2022 Sep:153:113319. doi: 10.1016/j.biopha.2022.113319.
Zhiyuan Zheng 1,  Ting Xu 1,  Zhiyan Liu 1,  Wenyue Tian 1,  Zhi-Hong Jiang 2,  Guo-Yuan Zhu 2,  Ting Li 1,  Jin Gao 3,  Li-Ping Bai 4
Affiliations

Affiliations

  • 1 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.
  • 2 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; Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease (Macau University of Science and Technology), 999078, Macau, People's Republic of China.
  • 3 IncreasePharm (Hengqin) Institute Co., Ltd, Zhu Hai, Guangdong 519031, People's Republic of China.
  • 4 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; Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease (Macau University of Science and Technology), 999078, Macau, People's Republic of China. Electronic address: [email protected].
PMID: 35753261 DOI: 10.1016/j.biopha.2022.113319
Abstract

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.

Keywords

Breast cancer; Cryptolepine (CLP); Glycolysis; Hypoxia inducible factor-1 (HIF-1).

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