Worenine reverses the Warburg effect and inhibits colon cancer cell growth by negatively regulating HIF-1α

Ji, Lijiang; Shen, Weixing; Zhang, Feng; Qian, Jie; Jiang, Jie; Weng, Li-Ping; Tan, Jun; Li, Liu; Chen, Yugen; Cheng, Haibo; Sun, Dongdong

doi:10.1186/s11658-021-00263-y

Cited by 24 publications

(20 citation statements)

References 28 publications

(35 reference statements)

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“…Worenine inhibits cell viability and proliferation, as well as induces G 2 /M phase arrest by balancing the Warburg effect via HIF-1α signaling in CRC cells ( Ji L. J. et al, 2021 ).…”

Section: Antitumor Effects and Corresponding Mechanismsmentioning

confidence: 99%

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers

Chen

Liang

et al. 2022

Front. Pharmacol.

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Cancer is a serious disease with an increasing number of reported cases and high mortality worldwide. Gastrointestinal cancer defines a group of cancers in the digestive system, e.g., liver cancer, colorectal cancer, and gastric cancer. Coptidis Rhizoma (C. Rhizoma; Huanglian, in Chinese) is a classical Chinese medicinal botanical drug for the treatment of gastrointestinal disorders and has been shown to have a wide variety of pharmacological activity, including antifungal, antivirus, anticancer, antidiabetic, hypoglycemic, and cardioprotective effects. Recent studies on C. Rhizoma present significant progress on its anticancer effects and the corresponding mechanisms as well as its clinical applications. Herein, keywords related to C. Rhizoma, cancer, gastrointestinal cancer, and omics were searched in PubMed and the Web of Science databases, and more than three hundred recent publications were reviewed and discussed. C. Rhizoma extract along with its main components, berberine, palmatine, coptisine, magnoflorine, jatrorrhizine, epiberberine, oxyepiberberine, oxyberberine, dihydroberberine, columbamine, limonin, and derivatives, are reviewed. We describe novel and classic anticancer mechanisms from various perspectives of pharmacology, pharmaceutical chemistry, and pharmaceutics. Researchers have transformed the chemical structures and drug delivery systems of these components to obtain better efficacy and bioavailability of C. Rhizoma. Furthermore, C. Rhizoma in combination with other drugs and their clinical application are also summarized. Taken together, C. Rhizoma has broad prospects as a potential adjuvant candidate against cancers, making it reasonable to conduct additional preclinical studies and clinical trials in gastrointestinal cancer in the future.

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“…Worenine inhibits cell viability and proliferation, as well as induces G 2 /M phase arrest by balancing the Warburg effect via HIF-1α signaling in CRC cells ( Ji L. J. et al, 2021 ).…”

Section: Antitumor Effects and Corresponding Mechanismsmentioning

confidence: 99%

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers

Chen

Liang

et al. 2022

Front. Pharmacol.

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“…Kaempferol, present in Ginseng Radix et Rhizoma and Radix Scutellariae, exerts anti-inflammatory and antitumour effects by inhibiting inflammatory factors [ 58 ]. Worenine is a major active component of Coptidis Rhizoma, which inhibits colorectal cancer cell growth by negatively regulating HIF-1 α [ 59 ]. Moreover, the molecular docking results revealed that the five abovementioned major compounds of GJHQHLRSD had a high binding affinity to the EGFR in the tyrosine kinase inhibitor signaling pathway ( Figure 7 ).…”

Section: Discussionmentioning

confidence: 99%

Active Ingredients and Potential Mechanisms of the Gan Jiang-Huang Qin-Huang Lian-Ren Shen Decoction against Ulcerative Colitis: A Network Pharmacology and Molecular Docking-Based Study

Zhou

Zhang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Ulcerative colitis (UC), a chronic and nonspecific inflammatory bowel disease, seriously affects the quality of patients’ life. Han Re Bing Yong Fa (treating diseases with both cool- and warm-natured herbs) is a classical therapeutic principle of traditional Chinese medicine (TCM), which is often used to treat chronic diseases, including UC. The Gan Jiang-Huang Qin-Huang Lian-Ren Shen decoction (GJHQHLRSD), a representative of Han Re Bing Yong Fa, is effective in alleviating inflammatory symptoms in UC. However, the pharmacological mechanism underlying its anti-inflammatory effect remains unclear. Methods. A network pharmacology strategy, including the construction and analysis of the drug–disease network, was used to explore the complex mechanism of GJHQHLRSD treatment of UC. In addition, molecular docking technology was used to preliminarily examine the binding ability of the potential active components and core therapeutic targets of GJHQHLRSD. Results. The network pharmacology results revealed 140 targets of GJHQHLRSD which are involved in UC. The PPI network analysis identified seven target genes: BCL2L1, NR3C1, ALOX5, S1PR5, NR1I2, CYP2D6, and LPAR6. The molecular docking results revealed that the following displayed strongest combined effects: EGFR with kaempferol, ERK1 with worenine, STAT3 with Palmidin A, BCL2L1 with diop and VEGFA with ginsenoside Rg3. The KEGG and gene ontology enrichment analyses results indicated that GJHQHLRSD functions by regulating the EGFR signaling pathway in UC treatment. Other effective biological processes involved in UC treatment included cancer-related as well as inflammation and viral infection signaling pathways, such as the “MicroRNAs in cancer,” “TNF signaling pathway,” and “JAK-STAT signaling pathway.” Conclusions. This study reflects the multicomponent, multitarget, and multipathway characteristics of the action mechanism of GJHQHLRSD in treating UC. Furthermore, it helps better understand the TCM therapeutic principle of Han Re Bing Yong Fa and explore novel candidate drug targets for UC treatment.

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“…Overexpression of HIF-1α has been demonstrated to play a significant role in the development and progression of multiple cancers [ 116 – 118 ]. In a recent study by Shao et al [ 38 ], the effect of metformin on HIF-1α in the breast cancer TME was assessed.…”

Section: Metformin and Cancer Therapymentioning

confidence: 99%

The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors

2022

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Tumor-infiltrated lymphocytes are exposed to many toxic metabolites and molecules in the tumor microenvironment (TME) that suppress their anti-tumor activity. Toxic metabolites, such as lactate and ketone bodies, are produced mainly by catabolic cancer-associated fibroblasts (CAFs) to feed anabolic cancer cells. These catabolic and anabolic cells make a metabolic compartment through which high-energy metabolites like lactate can be transferred via the monocarboxylate transporter channel 4. Moreover, a decrease in molecules, including caveolin-1, has been reported to cause deep metabolic changes in normal fibroblasts toward myofibroblast differentiation. In this context, metformin is a promising drug in cancer therapy due to its effect on oncogenic signal transduction pathways, leading to the inhibition of tumor proliferation and downregulation of key oncometabolites like lactate and succinate. The cross-feeding and metabolic coupling of CAFs and tumor cells are also affected by metformin. Therefore, the importance of metabolic reprogramming of stromal cells and also the pivotal effects of metformin on TME and oncometabolites signaling pathways have been reviewed in this study.

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Worenine reverses the Warburg effect and inhibits colon cancer cell growth by negatively regulating HIF-1α

Cited by 24 publications

References 28 publications

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers

Active Ingredients and Potential Mechanisms of the Gan Jiang-Huang Qin-Huang Lian-Ren Shen Decoction against Ulcerative Colitis: A Network Pharmacology and Molecular Docking-Based Study

The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors

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