Parthenolide Derivatives as PKM2 Activators Showing Potential in Colorectal Cancer

Liu, Xingchen; Wang, Cheng; Li, Shang; Qu, Lailiang; Yin, Fucheng; Lu, Dehua; Luo, Heng; Chen, Xinye; Luo, Zhongwen; Cui, Ningjie; Wang, Xiaobing

doi:10.1021/acs.jmedchem.1c01380

Cited by 14 publications

(10 citation statements)

References 41 publications

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“…It is an NF- κB inhibitor, that inhibits histone deacetylase 1 (HDAC-1) and DNA methyltransferase 1 (DMT-1) ( Bork et al, 1997 ; Freund et al, 2020 ). It has also been found to have anti-cancer activity in a variety of tumors, such as breast tumors, colorectal cancer, renal cell carcinoma, and et al ( Araújo et al, 2020 ; Liu D. et al, 2021 ; Liu X. et al, 2021 ). Combination treatment with Parthenolide and 5-FU provides synergistic anti-cancer effects in vitro and in vivo ( Kim S.-L. et al, 2013 ; Liu Dajun et al, 2013 ; Ding et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Generation of multicellular tumor spheroids with micro-well array for anticancer drug combination screening based on a valuable biomarker of hepatocellular carcinoma

Wang

Liu

Yin

et al. 2022

Front. Bioeng. Biotechnol.

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Hepatocellular carcinoma (HCC) is a highly malignant tumor with a poor prognosis. More than 30% of patients with diagnosed HCC have abnormally high expression of fibroblast growth factor receptor 4 (FGFR4). Currently, clinical trials for a variety of FGFR4-specific inhibitors have started. However, the effect of these inhibitors is not ideal, and it is necessary to find a drug combination to synergistically exert anti-tumor effects. We found strong correlations between FGFR4 and HCC clinicopathological characteristics in the present study. After grouping patients according to FGFR4 expression, the key gene signatures were inputted the drug-gene related databases, which predicted several potential drug candidates. More importantly, to achieve the reliable and high throughput drug cytotoxicity assessment, we developed an efficient and reproducible agarose hydrogel microwells to generate uniform-sized multicellular tumor spheroids, which provide better mimicry of conventional solid tumors that can precisely represent anticancer drug candidates’ effects. Using high content screening, we quickly evaluated the enhanced anti-tumor effects of these combinations. Finally, we demonstrated that Parthenolide is a potential drug that can significantly enhance the clinical efficacy of FGFR4 receptor inhibitors. In general, we offered a new therapeutic way for FGFR4 positive HCC patients.

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Section: Discussionmentioning

confidence: 99%

Generation of multicellular tumor spheroids with micro-well array for anticancer drug combination screening based on a valuable biomarker of hepatocellular carcinoma

Wang

Liu

Yin

et al. 2022

Front. Bioeng. Biotechnol.

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“…Also, PKM2 is extensively expressed in colorectal cancer to support energy and biosynthetic needs. Liu et al (2021) discovered the effect of parthenolide derivatives on colorectal cancer (HT29 and SW480) cells. It is noted that parthenolide derivatives decreased the expression of total PKM2, prevented nucleus translocation of PKM2 dimer, and inhibited the PKM2/STAT3 signaling pathway by binding with Cys424 of PKM2 in HT29 and SW480 cells.…”

Section: Natural Product Inhibitors Of Pkm2mentioning

confidence: 99%

“…PKM2 and reduced nucleus translocation of PKM2 in glioblastoma cells without an influence on the expression of total PKM2, thereby inhibiting the STAT3 signal pathway in glioblastoma. Also, PKM2 is extensively expressed in colorectal cancer to support energy and biosynthetic needs Liu et al (2021). discovered the effect of parthenolide derivatives on colorectal cancer (HT29 and SW480) cells.…”

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confidence: 99%

Cancer metabolism control by natural products: Pyruvate kinase M2 targeting therapeutics

El‐Far

Jaouni

et al. 2022

Phytotherapy Research

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Glycolysis is the primary source of energy for cancer growth and metastasis. The shift in metabolism from mitochondrial oxidative phosphorylation to aerobic glycolysis is called the Warburg effect. Cancer progression due to aerobic glycolysis is often associated with the activation of oncogenes or the loss of tumor suppressors. Therefore, inhibition of glycolysis is one of the effective strategies in cancer control. Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme overexpressed in breast, prostate, lung, colorectal, and liver cancers. Here, we discuss published studies regarding PKM2 inhibitors from natural products that are promising drug candidates for cancer therapy. We have highlighted the potential of natural PKM2 inhibitors for various cancer types. Moreover, we encourage researchers to evaluate the combinational effects between natural and synthetic PKM2 inhibitors. Also, further high‐quality studies are needed to firmly establish the clinical efficacy of natural products.

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“…1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) downregulated the GAPDH-dependent glycolysis pathway in LPS-stimulated macrophages, which represents a novel class of GAPDH inhibitors ( Li et al, 2022a ). Parthenolide was identified as a moderate activator of PKM2, a vital kinase in the glycolysis system, and showed significant anti-Glioblastoma multiforme activity and significantly suppressed tumor growth in the HT29 xenograft model ( Ding et al, 2020 ; Liu X. et al, 2021 ). Dioscin, a natural steroid saponin derived from several plants, significantly inhibited glycolysis in colorectal cancer cells growth through regulating Cdh1-mediated F-box protein Skp2 degradation ( Zhou et al, 2020 ).…”

Section: Natural Products Targeting Glycolysis In Cancermentioning

confidence: 99%

Natural products targeting glycolysis in cancer

et al. 2022

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Many energy metabolism pathways exist in cancer, including glycolysis, amino acid metabolism, fatty acid oxidation, and mitochondrial respiration. Tumor cells mainly generate energy through glycolysis to maintain growth and biosynthesis of tumor cells under aerobic conditions. Natural products regulate many steps in glycolysis and targeting glycolysis using natural products is a promising approach to cancer treatment. In this review, we exemplify the relationship between glycolysis and tumors, demonstrate the natural products that have been discovered to target glycolysis for cancer treatment and clarify the mechanisms involved in their actions. Natural products, such as resveratrol mostly found in red grape skin, licochalcone A derived from root of Glycyrrhiza inflate, and brusatol found in Brucea javanica and Brucea mollis, largely derived from plant or animal material, can affect glycolysis pathways in cancer by targeting glycolytic enzymes and related proteins, oncogenes, and numerous glycolytic signal proteins. Knowledge of how natural products regulate aerobic glycolysis will help illuminate the mechanisms by which these products can be used as therapeutics to inhibit cancer cell growth and regulate cellular metabolism.Systematic Review Registration: https://pubmed.ncbi.nlm.nih.gov/, https://clinicaltrials.gov/, http://lib.zzu.edu.cn/

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Parthenolide Derivatives as PKM2 Activators Showing Potential in Colorectal Cancer

Cited by 14 publications

References 41 publications

Generation of multicellular tumor spheroids with micro-well array for anticancer drug combination screening based on a valuable biomarker of hepatocellular carcinoma

Generation of multicellular tumor spheroids with micro-well array for anticancer drug combination screening based on a valuable biomarker of hepatocellular carcinoma

Cancer metabolism control by natural products: Pyruvate kinase M2 targeting therapeutics

Natural products targeting glycolysis in cancer

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