Gambogic acid sensitizes gemcitabine efficacy in pancreatic cancer by reducing the expression of ribonucleotide reductase subunit-M2 (RRM2)

Xia, Guanggai; Wang, Hongcheng; Song, Ziliang; Meng, Qingcai; Huang, Xiuyan; Huang, Xinyu

doi:10.1186/s13046-017-0579-0

Cited by 75 publications

(65 citation statements)

References 52 publications

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“…Nampt inhibitor (FK866) reversed this resistance to sensitivity [53]. Additionally, gemcitabine also promotes the expression of the ribonucleotide reductase M2 (RRM2) subunit in pancreatic cancer cells through the ERK/E2F1 pathway, promoting deoxyribonucleotide biosynthesis and inhibiting gemcitabine-induced DNA damage [153,154]. CG-5, a glucose transporter inhibitor, inhibits E2F1 expression and enhances gemcitabine efficacy in pancreatic cancer cells [153].…”

Section: Chemoresistance and Metabolismmentioning

confidence: 99%

Metabolism of pancreatic cancer: paving the way to better anticancer strategies

et al. 2020

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Pancreatic cancer is currently one of the most lethal diseases. In recent years, increasing evidence has shown that reprogrammed metabolism may play a critical role in the carcinogenesis, progression, treatment and prognosis of pancreatic cancer. Affected by internal or external factors, pancreatic cancer cells adopt extensively distinct metabolic processes to meet their demand for growth. Rewired glucose, amino acid and lipid metabolism and metabolic crosstalk within the tumor microenvironment contribute to unlimited pancreatic tumor progression. In addition, the metabolic reprogramming involved in pancreatic cancer resistance is also closely related to chemotherapy, radiotherapy and immunotherapy, and results in a poor prognosis. Reflective of the key role of metabolism, the number of preclinical and clinical trials about metabolism-targeted therapies for pancreatic cancer is increasing. The poor prognosis of pancreatic cancer patients might be largely improved after employing therapies that regulate metabolism. Thus, investigations of metabolism not only benefit the understanding of carcinogenesis and cancer progression but also provide new insights for treatments against pancreatic cancer.

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Section: Chemoresistance and Metabolismmentioning

confidence: 99%

Metabolism of pancreatic cancer: paving the way to better anticancer strategies

et al. 2020

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“…The combination of GA and other chemotherapy agents has been widely used to improve the therapeutic effects against various cancers such as osteosarcoma, pancreatic and lung cancers [639,653,663,664]. Cisplatin resistance is a main clinical problem for the treatment of lung cancer, and the treatment of cisplatin with GA is shown to enhance apoptosis and decrease the cisplatin resistance index in human NSCLC cisplatin-resistance A549/ DDP cells [663].…”

Section: Gambogic Acid (Ga)mentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including antiproliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

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“…Previous studies have revealed that ZFP36 is a downstream gene in the EGFR and ERK signaling pathway [32], which is also required for the self-renewal of cancer stem cells in addition to regulating proliferation and survival [31]. KEGG pathway analyses and related studies have reported that GA can downregulate the EGFR and ERK signaling pathway [46]. Furthermore, our results revealed that GA could increase the expression of ZFP36 by inhibiting the EGFR/ERK signaling pathway.…”

Section: Discussionmentioning

confidence: 56%

Gambogic Acid Efficiently Kills Stem-Like Colorectal Cancer Cells by Upregulating ZFP36 Expression

Fang

Zhang

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Gambogic acid (GA), the main active compound of Gamboge hanburyi, has been reported to be a potential novel antitumor drug. Whether GA inhibits putative cancer stem cells (CSCs), which are considered to be the major cause of cancer treatment failure, remains largely unknown. This study investigated whether GA inhibits the CSCs of colorectal cancer (CRC) and its possible mechanisms. Methods: We performed CCK8 and tumor sphere formation assays, percentage analysis of both side population and CD133⁺CD44⁺ cells, and the detection of stem cells markers, in order to assess the role of GA in inhibiting the stem celllike features of CRC. An mRNA microarray was performed to identify the downstream gene affected by GA and rescue assays were performed to further clarify whether the downstream gene is involved in the GA induced decrease of the stem cell-like CRC population. CRC cells were engineered with a CSC detector vector encoding GFP and luciferase (Luc) under the control of the Nanog promoter, which were utilized to investigate the effect of GA on putative CSC in human tumor xenograft-bearing mice using in vivo bioluminescence imaging. Results: Our results showed that GA significantly reduced tumor sphere formation and the percentages of side population and CD133⁺CD44⁺ cells, while also decreasing the expression of stemness and EMT-associated markers in CRC cells in vitro. GA killed stem-like CRC cells by upregulating the expression of ZFP36, which is dependent on the inactivation of the EGFR/ ERK signaling pathway. GFP+ cells harboring the P_Nanog-GFP-T2A-Luc transgene exhibited CSC characteristics. The in vivo results showed that GA significantly inhibited tumor growth in nude mice, accompanied by a remarkable reduction in the putative CSC number, based on whole-body bioluminescence imaging. Conclusion: These findings suggest that GA significantly inhibits putative CSCs of CRC both in vitro and in vivo by inhibiting the activation of the EGFR/ ERK/ZFP36 signaling pathway and may be an effective drug candidate for anticancer therapies.

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Gambogic acid sensitizes gemcitabine efficacy in pancreatic cancer by reducing the expression of ribonucleotide reductase subunit-M2 (RRM2)

Cited by 75 publications

References 52 publications

Metabolism of pancreatic cancer: paving the way to better anticancer strategies

Metabolism of pancreatic cancer: paving the way to better anticancer strategies

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Gambogic Acid Efficiently Kills Stem-Like Colorectal Cancer Cells by Upregulating ZFP36 Expression

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