Article
Biochemistry & Molecular Biology
Yudi Ma, Xiaohui Lai, Zhongling Wen, Ziling Zhou, Minkai Yang, Qingqing Chen, Xuan Wang, Feng Mei, Liu Yang, Tongming Yin, Shucun Sun, Guihua Lu, Jinliang Qi, Hongyan Lin, Hongwei Han, Yonghua Yang
Summary: The Warburg effect is essential for tumor proliferation, but reversing it can lead to a novel anti-cancer strategy. Two key enzymes in tumor glucose metabolism pathway, PKM2 and PDK1, not only contribute to the Warburg effect, but also serve as druggable targets for CRC. A series of benzenesulfonyl shikonin derivatives were designed to simultaneously regulate PKM2 and PDK1. Among them, compound Z10 acted as a PKM2 activator and PDK1 inhibitor, significantly inhibiting glycolysis and remodeling tumor metabolism. In addition, Z10 inhibited CRC cell proliferation and migration, and induced apoptosis. Furthermore, Z10 showed in vivo anti-tumor activity with lower toxicity compared to shikonin. Our findings suggest that altering tumor energy metabolism through multi-target synergies is feasible, and Z10 could be a potential anti-CRC agent.
BIOORGANIC CHEMISTRY
(2023)
Article
Cardiac & Cardiovascular Systems
Qinfeng Li, Chao Li, Abdallah Elnwasany, Gaurav Sharma, Yu A. An, Guangyu Zhang, Waleed M. Elhelaly, Jun Lin, Yingchao Gong, Guihao Chen, Meihui Wang, Shangang Zhao, Chongshan Dai, Charles D. Smart, Juan Liu, Xiang Luo, Yingfeng Deng, Lin Tan, Shuang-Jie Lv, Shawn M. Davidson, Jason W. Locasale, Philip L. Lorenzi, Craig R. Malloy, Thomas G. Gillette, Matthew G. Vander Heiden, Philipp E. Scherer, Luke I. Szweda, Guosheng Fu, Zhao V. Wang
Summary: PKM1 plays a crucial role in maintaining a homeostatic response in the heart under hemodynamic stress, protecting against cardiac dysfunction and fibrosis caused by pressure overload. Furthermore, PKM1 is essential for enhancing glycolytic flux, mitochondrial respiration, and ATP production under pressure overload at a mechanistic level.
Review
Immunology
Chan Li, Fang-Yuan Liu, Ying Shen, Yuan Tian, Feng-Juan Han
Summary: This paper discusses the importance of glycolysis in cancer cells, particularly in ovarian cancer. Glycolysis plays a crucial role in promoting energy production and cancer progression. Understanding the relationship between glycolysis and related molecular mechanisms may provide new strategies for the treatment of ovarian cancer.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Qingqing Chen, Hongwei Han, Faxiang Lin, Liangjie Yang, Lu Feng, Xiaohui Lai, Zhongling Wen, Minkai Yang, Changyi Wang, Yudi Ma, Tongming Yin, Guihua Lu, Hongyan Lin, Jinliang Qi, Yonghua Yang
Summary: This study evaluated the anti-tumor activities of semi-synthesized shikonin (SK) derivatives against human breast cancer cells. The findings showed that these derivatives exhibited strong inhibition of cell proliferation and migration, and induced cell apoptosis through regulating apoptosis and glucose metabolism pathways.
Article
Chemistry, Multidisciplinary
Xiangling Ren, Xinyuan Huang, Qiong Wu, Longfei Tan, Changhui Fu, Yi Chen, Xianwei Meng
Summary: Metal organic frameworks were found to inhibit the activity of pyruvate kinase in tumor cells, with nanoscale ZIF-8 showing the ability to inhibit glycolysis. The inhibitory effect is attributed to the zinc ions in ZIF-8, which has an IC50 one percent of that of zinc ion. This novel enzyme inhibitor holds promise for cancer therapy.
CHINESE CHEMICAL LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Nives Skorja Milic, Klemen Dolinar, Katarina Mis, Urska Matkovic, Marusa Bizjak, Mojca Pavlin, Matej Podbregar, Sergej Pirkmajer
Summary: Inhibition of pyruvate dehydrogenase kinase (PDK) by Dichloroacetate (DCA) can reduce the abundance of PDK isoenzymes in a cell-type-specific manner via both transcriptional and post-transcriptional mechanisms. The differential response of PDK isoenzymes to DCA in cancer cells and muscle cells highlights the importance of understanding the pharmacological effects of DCA in different cell types.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Biao Xu, Zhi-Peng Wang, Qingwang Liu, Xiaohong Yang, Xuemin Li, Ding Huang, Yanfei Qiu, Kin Yip Tam, Shao-Lin Zhang, Yun He
Summary: This study reported a series of novel dichloroacetophenones as potent PDKs inhibitors, with compound 6u showing significant anti-proliferative effects on various cancer cells. In mouse models, 6u demonstrated potent antitumor activity without negative impact on body weight. The compound was also found to induce cancer cell apoptosis, arrest cell cycle progression, inhibit cell migration, and alter glucose metabolic pathways in cancer cells, showing potential as a modulator for reprogramming glycolysis in cancer cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Yiyu Qin, Yongliang Zheng, Cheng Huang, Yuanyuan Li, Min Gu, Qin Wu
Summary: The study revealed that miR-181b-5p is significantly upregulated in GBC tumor tissues and closely related to glycolysis. Inhibiting miR-181b-5p can reduce the viability and glycolysis of GBC cells under hypoxia.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yuning Wang, Bo Cao, Ruiyang Zhao, Hanghang Li, Bo Wei, Guanghai Dai
Summary: This study identified the novel circular RNA circBFAR as a promoter of gastric cancer cell proliferation through the miR-513a-3p/hexokinase 2 (HK2) axis, and its inhibition led to a significant decrease in glycolysis levels. It revealed a potentially new therapeutic target for personalized treatment in gastric cancer.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Cell Biology
Fanglong Wu, Shimeng Wang, Qingxiang Zeng, Junjiang Liu, Jin Yang, Jingtian Mu, Hongdang Xu, Lanyan Wu, Qinghong Gao, Xin He, Ying Liu, Hongmei Zhou
Summary: This study reveals that TGF-beta RII overexpression can suppress glucose metabolism in CAFs by attenuating PKM2 nuclear translocation, thereby inhibiting oral cancer tumor growth, providing a novel therapeutic approach for oral cancer treatment.
CELL DEATH DISCOVERY
(2022)
Article
Pharmacology & Pharmacy
Min Kyoung Cho, Ling Jin, Jung Ho Han, Jung-Suk Jin, Se-Yun Cheon, Su Shin, Sung-Jin Bae, Jang-Kyung Park, Ki-Tae Ha
Summary: Endometriosis is a chronic inflammatory disorder with limited treatment options. However, recent studies have shown that Prunella vulgaris, a traditional herbal medicine with anti-estrogenic effects, may be a potential treatment for endometriosis. In this study, water-extracted Prunella vulgaris was found to alleviate endometriosis in mice by inducing apoptosis in endometrial cells through the regulation of aerobic glycolysis enzymes. These findings suggest that Prunella vulgaris may be a promising candidate for the prevention and treatment of endometriosis.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Yuanyuan Chen, Yunfei Guo, Mei Yuan, Song Guo, Shuaishuai Cui, Dahu Chen
Summary: USP4 interacts with PKM2 and catalyzes the de-ubiquitination of PKM2. Overexpression of USP4 promotes cell proliferation, glucose uptake, and lactate production in gastric cancer cells. Knockdown of USP4 reduces PKM2 levels and results in a reduction in cell proliferation and the glycolysis rate.
Review
Biochemistry & Molecular Biology
Russel J. Reiter, Ramaswamy Sharma, Sergio Rosales-Corral
Summary: Glucose is a crucial nutrient for cells, but in some pathological cells, aerobic glycolysis may occur due to the inhibition of pyruvate dehydrogenase complex. Glycolytics like melatonin can convert diseased cells to a healthier phenotype by inhibiting hypoxia-inducible factor-1 alpha and promoting intramitochondrial conversion of pyruvate into acetyl coenzyme A, thus explaining its actions in inhibiting various diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jung Ho Han, MinJeong Kim, Hyeon Jin Kim, Se Bok Jang, Sung-Jin Bae, In-Kyu Lee, Dongryeol Ryu, Ki-Tae Ha
Summary: Resistance to anticancer therapeutics is a major challenge in cancer treatment, with altered cancer metabolism, such as the Warburg effect, playing a pivotal role. The use of antiglycolytic agents, such as catechin, may help overcome resistance to 5FU in gastric cancer cells by limiting LDHA expression and lactate production, providing a potential novel adjuvant drug option.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Daqian Xu, Fei Shao, Xueli Bian, Ying Meng, Tingbo Liang, Zhimin Lu
Summary: Key pathological signaling pathways regulate metabolic enzymes, giving them nonmetabolic functions. These aberrantly regulated metabolic enzymes play critical roles in governing cellular activities, promoting disease progression.