Article
Pharmacology & Pharmacy
Yun-zi Liu, Ming-yuan Xu, Xiao-yu Dai, Lang Yan, Lei Li, Rui-zhen Zhu, Li-jun Ren, Ji-qian-zhu Zhang, Xiao-fang Zhang, Jin-feng Li, Yi-jun Tian, Wen-jing Shi, Ye-qiang Liu, Chun-lei Jiang, Jiang-bo Zhu, Ji-kuai Chen
Summary: PKM2, highly expressed in psoriatic epidermis, plays a crucial role in promoting glycolytic metabolism and cell proliferation in psoriatic keratinocytes. Inhibition of PKM2 or glycolysis effectively suppresses keratinocyte proliferation, suggesting PKM2 as a potential therapeutic target for psoriasis.
FRONTIERS IN PHARMACOLOGY
(2021)
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)
Review
Chemistry, Medicinal
Ali H. El-Far, Soad K. Al Jaouni, Xiaotao Li, Junjiang Fu
Summary: Glycolysis is a primary energy source for cancer growth and metastasis, and inhibiting glycolysis is an effective cancer control strategy. PKM2, a key glycolytic enzyme, is overexpressed in various cancer types, and natural PKM2 inhibitors have potential therapeutic effects.
PHYTOTHERAPY RESEARCH
(2022)
Article
Oncology
Kaili Cui, Haili Wu, Lichao Zhang, Hanqing Li, Ghani Israr, Zhuoyu Li
Summary: In this study, a novel lncRNA 495810 was found to be significantly upregulated in colon cancer and correlated with poor prognosis in patients. The highly expressed lncRNA 495810 promoted cell proliferation and inhibited apoptosis in colon cancer cells. It was also found that lncRNA 495810 interacted with PKM2 protein and enhanced PKM2 protein stability via the ubiquitin-proteasome pathway. These findings suggest that lncRNA 495810 is a potential biomarker for predicting prognosis and a therapeutic target for colon cancer.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2023)
Article
Medicine, Research & Experimental
Shuya Mei, Qiaoyi Xu, Yue Hu, Ri Tang, Jinhua Feng, Yang Zhou, Shunpeng Xing, Yuan Gao, Zhengyu He
Summary: This study found that the integrin beta 3-PKM2 pathway-mediated aerobic glycolysis is involved in mechanical ventilation-induced pulmonary fibrosis. Inhibiting aerobic glycolysis targeting the integrin beta 3-PKM2 pathway may be a promising treatment for mechanical ventilation-induced pulmonary fibrosis.
Article
Pharmacology & Pharmacy
Eunhwan Kim, Yumi Hwang, Heejene Kim, Geon-Uk Kim, Yeong Chan Ryu, Minguen Yoon, Kang-Yell Choi
Summary: In this study, the researchers found that the activation of the Wnt/beta-catenin signaling pathway increases PKM2 expression and pyruvate kinase (PK) activity during wound healing in mice. They also discovered that the allosteric activator of PKM2, TEPP-46, enhances keratinocyte migration and wound healing. Furthermore, the combination of TEPP-46 and a Wnt/beta-catenin signaling activator, KY19382, significantly accelerates wound healing and induces angiogenesis in the wound beds.
Review
Biochemistry & Molecular Biology
J. R. Dev Arundhathi, Sandeep R. Mathur, Ajay Gogia, S. V. S. Deo, Purusottam Mohapatra, Chandra Prakash Prasad
Summary: Triple negative breast cancer (TNBC) has the worst prognosis among breast cancer subtypes and standard chemotherapy is the main treatment. Metabolic reprogramming, specifically altered glycolysis, plays a crucial role in TNBC progression, offering potential therapeutic targets.
MOLECULAR BIOLOGY REPORTS
(2021)
Article
Oncology
Bi Wang, Yingnan Yuan, Yin Zou, Zhengjun Qi, Guijia Huang, Yi Liu, Shan Xia, Yu Huang, Zhi Huang
Summary: Growing evidence supports the important role of aerobic glycolysis in cervical cancer. This study reveals that FBP2 plays a role in cervical cancer progression by inhibiting aerobic glycolysis through inducing PKM2 ubiquitination.
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.
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
Oncology
Fadi Almouhanna, Biljana Blagojevic, Suzan Can, Ali Ghanem, Stefan Woelfl
Summary: The study investigates the potential effects of the pyruvate kinase isozyme (M2) allosteric activator (DASA-58) on glucose rewiring in breast cancer cells. DASA-58 is shown to induce pyruvate kinase activity without affecting overall cell survival, reduce TXNIP levels, and modulate AMPK phosphorylation, making breast cancer cells more susceptible to other therapeutics.
CANCER & METABOLISM
(2021)
Article
Geriatrics & Gerontology
Xue Li, Lin-Lin Luo, Rui-Feng Li, Chun-Lin Chen, Min Sun, Sen Lin
Summary: Lens fibrosis is a common cause of cataract in elderly individuals. This study explored the role of pantothenate kinase 4 (PANK4) and glycolytic metabolism in lens epithelial-mesenchymal transition (EMT). PANK4 levels were associated with aging and loss of function of PANK4 alleviated LEC EMT by promoting glycolysis. The PANK4-PKM2 axis was found to regulate EMT and HIF-1 stabilization, offering potential insights for fibrosis treatment in other organs.
Article
Biochemistry & Molecular Biology
Lei Na, Zhuo Wang, Yu Bai, Yu Sun, Dan Dong, Wei Wang, Chenghai Zhao
Summary: This study identified that WNT7B is downregulated in high-grade bladder urothelial carcinomas, and its low expression is associated with poor prognosis. WNT7B inhibits bladder urothelial carcinoma progression by suppressing EMT, stem-like properties, and chemoresistance.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Xueyan Sun, Yijiao Peng, Jingduo Zhao, Zhizhong Xie, Xiaoyong Lei, Guotao Tang
Summary: Tumor cells primarily rely on aerobic glycolysis for energy, and inhibiting the three main rate-limiting enzymes in glycolysis is considered an important strategy for cancer treatment. The development of inhibitors targeting these enzymes is a focus of research for potential therapeutic interventions.
BIOORGANIC CHEMISTRY
(2021)
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)
