Discovery of Myricetin as a Potent Inhibitor of Human Flap Endonuclease 1, Which Potentially Can Be Used as Sensitizing Agent against HT-29 Human Colon Cancer Cells

Ma, Long; Cao, Xiwang; Wang, Haiyue; Lu, Kui; Wáng, Ying; Tu, Chun‐Hao; Dai, Yujie; Meng, Yuanyuan; Li, Yuyin; Yu, Peng; Diao, Aipo

doi:10.1021/acs.jafc.8b05447

Cited by 55 publications

(37 citation statements)

References 49 publications

(25 reference statements)

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“…This study suggested that myricetin can be utilized for the design of therapeutic agents against human colon cancer. Myricetin also acts as a potent inhibitor of human flap endonuclease 1 (hFEN1) protein (IC 50 690 nM), based on inhibitory mechanisms, molecular docking, and cancer cell-based assays [128]. The hFEN1 protein is a functional member of the 5′-nuclease superfamily.…”

Section: Parkinson Diseasementioning

confidence: 99%

Myricetin bioactive effects: moving from preclinical evidence to potential clinical applications

Taheri

Suleria

Martins

et al. 2020

BMC Complement Med Ther

132

112

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Several flavonoids have been recognized as nutraceuticals, and myricetin is a good example. Myricetin is commonly found in plants and their antimicrobial and antioxidant activities is well demonstrated. One of its beneficial biological effects is the neuroprotective activity, showing preclinical activities on Alzheimer, Parkinson, and Huntington diseases, and even in amyotrophic lateral sclerosis. Also, myricetin has revealed other biological activities, among them as antidiabetic, anticancer, immunomodulatory, cardiovascular, analgesic and antihypertensive. However, few clinical trials have been performed using myricetin as nutraceutical. Thus, this review provides new insights on myricetin preclinical pharmacological activities, and role in selected clinical trials.

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Section: Parkinson Diseasementioning

confidence: 99%

Myricetin bioactive effects: moving from preclinical evidence to potential clinical applications

Taheri

Suleria

Martins

et al. 2020

BMC Complement Med Ther

132

112

View full text Add to dashboard Cite

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“…8 Moreover, FEN1 is considered a marker for metastasis and poor prognosis in multiple cancers; [9][10][11] additionally, recent studies have revealed that FEN1 has a role in regulating sensitivity to chemotherapy. 12,13 Autophagy is a stress-relieving/homeostatic cellular recycling process involved in the maintenance of cellular homeostasis through the lysosomal degradation of various proteins and damaged organelles. 14 Accumulating evidence has shown that autophagy can promote survival in patients undergoing chemotherapy, radiotherapy, and targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

<p>miR-193b Increases the Chemosensitivity of Osteosarcoma Cells by Promoting FEN1-Mediated Autophagy</p>

Dong¹,

Ye²,

Ma³

et al. 2019

OTT

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Background: Osteosarcoma (OS) is one of the most common malignant bone tumors and specific microRNAs (miRNAs) are closely associated with malignant OS progression. In this study, we examined the role of and the involvement of autophagy and apoptosis in the chemosensitivity of OS cells. Methods: We employed qRT-PCR, Western blot, and immunohistochemistry to examine the expression levels of miR-193b, flap endonuclease 1 (FEN1), and autophagy-related proteins. Apoptosis was determined by flow cytometry using an Annexin V-FITC/PI apoptosis detection kit. Luciferase reporter assays confirmed the relationship between miR-193b and FEN1. Results: miR-193b was downregulated in OS compared to adjacent normal tissues (p < 0.05). miR-193b overexpression in the OS cell lines induced autophagy and apoptosis, as shown by Western blotting and flow cytometry. Knockdown of FEN1, a structure-specific nuclease overexpressed in OS tissues (p < 0.001), induced apoptosis through activation of autophagy. Luciferase reporter assays confirmed that FEN1 is a direct target of miR-193b, FEN1 knockdown reinforced miR-193b induced apoptosis. Moreover, miR-193b expression enhanced epirubicin-induced autophagy and apoptosis. Conclusion: Collectively, the results showed that miR-193b/FEN1 may serve as a novel therapeutic target for OS aimed mainly at the induction of autophagy and apoptosis. The miR-193b/FEN1 axis increased the chemosensitivity of OS cells, while activation of autophagy enhanced the anticancer effects of epirubicin.

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“…[22] Among them, DNA damage repair is a new and important mechanism of tumor drug resistance and it is also a hottopic at present. Recent studies have shown that the BER activity as an important pathway of DNA damage repair is related to the chemotherapy sensitivity, and the studies of FEN1 have been widely concerne d [23][24][25]. Multiple studies have demonstrated that high FEN1 expression is associated with drug resistance in a variety of malignancies.…”

Section: Discussionmentioning

confidence: 99%

Jianpi-yangwei decoction inhibits DNA damage repair in the drug resistance of gastric cancer by reducing FEN1 expression

Huang

Tang

Fang

et al. 2020

BMC Complement Med Ther

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Background: Flap Endonuclease 1(FEN1) has been considered as a new tumor marker in recent years and Jianpi Yangwei Decoction (JPYW) is a basic Traditional Chinese Medicine (TCM) for the treatment of gastric cancer. This study aimed to explore the role of FEN1-mediated DNA damage repair in the drug resistance of gastric cancer and the effect of JPYW on it by employing BGC823/5-Fu drug-resistant cell model. Methods: The DNA repair efficiency of BGC823 and BGC823/5-Fu was compared intracellularly and extracellularly using an extrachromosomal assay system and the reconstituted base excision repair assay. By comparing gene and protein expression and identifying cell survival rates after knockdown or high expression of FEN1, the correlation between FEN1 high expression and 5-Fluorouracil (5-Fu) drug resistance was revealed. The effect of JPYW on DNA damage repair and FEN1 expression was observed by the degree of γ-H2AX phosphorylation in the cells, DNA repair efficiency and enzyme activity, et al. Results: BGC823/5-Fu had a higher DNA repair efficiency than BGC823(P < 0.001), which proved to be both intracellular and extracellular. FEN1 was highly expressed in BGC823/5-Fu regardless of gene level(P < 0.001) or protein level. Furthermore, manipulating FEN1 altered the sensitivity of cancer cells to chemotherapeutic drug 5-Fu. Different concentrations of JPYW were used to investigate the inhibitory effect on the expression of FEN1 and DNA damage repair. JPYW inhibited DNA damage repair both intracellularly and extracellularly: the phosphorylation of γ-H2AX increased, with more DNA damage in the cells; the synthetic 8-oxo dG damage repair was reduced; and the ability of cell lysates to repair DNA damage decreased. The decrease of FEN1 expression in BGC823/5-Fu had a concentration dependent relationship with JYPW. In addition, JPYW inhibited the activity of FEN1 at the enzymatic level, as the amount of cutoff synthetic 32 p labeled DNA substrates were decreased. Conclusion: FEN1 was highly expressed in drug-resistance gastric cancer cells BGC823/5-Fu, which leading to BGC823 resistant to (5-Fu) by acting on DNA damage repair. JPYW inhibited DNA damage repair and reversed 5-Fu drug resistance by reducing FEN1 expression and inhibiting FEN1 functional activity.

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Discovery of Myricetin as a Potent Inhibitor of Human Flap Endonuclease 1, Which Potentially Can Be Used as Sensitizing Agent against HT-29 Human Colon Cancer Cells

Cited by 55 publications

References 49 publications

Myricetin bioactive effects: moving from preclinical evidence to potential clinical applications

Myricetin bioactive effects: moving from preclinical evidence to potential clinical applications

<p>miR-193b Increases the Chemosensitivity of Osteosarcoma Cells by Promoting FEN1-Mediated Autophagy</p>

Jianpi-yangwei decoction inhibits DNA damage repair in the drug resistance of gastric cancer by reducing FEN1 expression

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