Dihydromyricetin reverses MRP2-induced multidrug resistance by preventing NF-κB-Nrf2 signaling in colorectal cancer cell

Wang, Ziyuan; Sun, Xiaoting; Feng, Yuanyuan; Wang, Yang; Zhang, Lu; Wang, Yan; Fang, Zhen; Azami, Nisma Lena Bahaji; Sun, Mingyu; Li, Qi

doi:10.1016/j.phymed.2020.153414

Cited by 39 publications

(24 citation statements)

References 44 publications

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“…One explanation for the anti-tumour role of Nrf2 relies on its antioxidant capacity, which renders tumour cells less sensitive to drugs that induce oxidative stress overcoming the typically high ROS threshold of tumours. Accordingly, many lines of evidence indicate that Nrf2 overactivity is implicated in chemoresistance to different conventional drugs including cisplatin [ 78 ], 5-fluorouracil [ 79 ], doxorubicin [ 80 ], vincristine [ 81 ], etoposide [ 82 ] and mitoxantrone [ 83 ].…”

Section: The Dual Role Of Nrf2 In Cancermentioning

confidence: 99%

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The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

Emanuele

Celesia

D’Anneo

et al. 2021

IJMS

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Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known transcription factor best recognised as one of the main regulators of the oxidative stress response. Beyond playing a crucial role in cell defence by transactivating cytoprotective genes encoding antioxidant and detoxifying enzymes, Nrf2 is also implicated in a wide network regulating anti-inflammatory response and metabolic reprogramming. Such a broad spectrum of actions renders the factor a key regulator of cell fate and a strategic player in the control of cell transformation and response to viral infections. The Nrf2 protective roles in normal cells account for its anti-tumour and anti-viral functions. However, Nrf2 overstimulation often occurs in tumour cells and a complex correlation of Nrf2 with cancer initiation and progression has been widely described. Therefore, if on one hand, Nrf2 has a dual role in cancer, on the other hand, the factor seems to display a univocal function in preventing inflammation and cytokine storm that occur under viral infections, specifically in coronavirus disease 19 (COVID-19). In such a variegate context, the present review aims to dissect the roles of Nrf2 in both cancer and COVID-19, two widespread diseases that represent a cause of major concern today. In particular, the review describes the molecular aspects of Nrf2 signalling in both pathological situations and the most recent findings about the advantages of Nrf2 inhibition or activation as possible strategies for cancer and COVID-19 treatment respectively.

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Section: The Dual Role Of Nrf2 In Cancermentioning

confidence: 99%

“…In this regard, a burst of recent literature has focused on compounds, many of which are natural, that are capable of inhibiting/downregulating Nrf2, thus overcoming chemoresistance [ 81 , 82 , 83 , 84 , 85 , 86 , 87 ].…”

Section: The Dual Role Of Nrf2 In Cancermentioning

confidence: 99%

The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

Emanuele

Celesia

D’Anneo

et al. 2021

IJMS

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“…Moreover, dihydromyricetin, a natural flavonoid from the leaves of Vitis heyneana , reversed MRP2-induced MDR by preventing NF-κB-Nrf2 signaling in colorectal cancer HCT116/OXA and HCT8/VCR cell lines [ 114 ]. Also, bavachinin, tephrosin, and candidone sensitized MDR MCF7/MX and EPG85.257RDB cells to daunorubicin and mitoxantrone [ 115 ].…”

Section: Anti-cancer Chemotherapy Resistancementioning

confidence: 99%

Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles

et al. 2021

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Cost-efficacy of currently applied treatments is an issue in overall cancer management challenging healthcare and causing tremendous economic burden to societies around the world. Consequently, complex treatment models presenting concepts of predictive diagnostics followed by targeted prevention and treatments tailored to the personal patient profiles earn global appreciation as benefiting the patient, healthcare economy, and the society at large. In this context, application of flavonoids as a spectrum of compounds and their nano-technologically created derivatives is extensively under consideration, due to their multi-faceted anti-cancer effects applicable to the overall cost-effective cancer management, primary, secondary, and even tertiary prevention. This article analyzes most recently updated data focused on the potent capacity of flavonoids to promote anti-cancer therapeutic effects and interprets all the collected research achievements in the frame-work of predictive, preventive, and personalized (3P) medicine. Main pillars considered are:- Predictable anti-neoplastic, immune-modulating, drug-sensitizing effects;- Targeted molecular pathways to improve therapeutic outcomes by increasing sensitivity of cancer cells and reversing their resistance towards currently applied therapeutic modalities.

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“…Dihydromyricetin (DHM), a biologically active avonoid compound from Ampelopsis grossedentata [7], exerts anti-in ammatory, hypoglycemic, antioxidative, antimicrobial, anti-allergic, and anti-acne effects [8]. Remarkably, this avonoid compound has attracted considerable attention because of its strong inhibitory effect on colorectal cancer [9], ovarian cancer [10], cholangiocarcinoma [11], and lung cancer [12]. It has been documented that DHM inhibited the progression of colorectal cancer and colon cancer in mouse models [9,13].…”

Section: Introductionmentioning

confidence: 99%

“…Remarkably, this avonoid compound has attracted considerable attention because of its strong inhibitory effect on colorectal cancer [9], ovarian cancer [10], cholangiocarcinoma [11], and lung cancer [12]. It has been documented that DHM inhibited the progression of colorectal cancer and colon cancer in mouse models [9,13]. Besides, DHM also plays an important role in various biological processes including cell proliferation, apoptosis, and migration [14].…”

Section: Introductionmentioning

confidence: 99%

Antitumor Effects of Dihydromyricetin on the Proliferation, Migration and Apoptosis of Human Hepatocellular Carcinoma Hep3B Cells

Jiang

et al. 2021

Preprint

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Background: Hepatocellular carcinoma (HCC) represents a serious public health problem worldwide and has high morbidity and mortality. Dihydromyricetin (DHM) exhibits anti-tumor effect on a variety of malignancies, but its antitumor function of DHM in HCC has been unclear. The aim of this study was designed to investigate the antitumor effect of DHM on cell apoptosis, proliferation, migration and invasion of hepatoma carcinoma cells. Methods: Cultured Hep3B cells were treated with different DHM concentrations, follow by cell apoptosis, proliferation, migration and invasion were examined by CCK-8, colony formation assay, wound healing, Transwell and flow cytometry, respectively. The mRNA and protein expression of apoptosis-associated genes and Bcl-2/Caspase-9 signaling pathway were validated by RT-PCR and western blot. Results: DHM markedly suppressed proliferation, migration, invasion and facilitated apoptosis in Hep3B cells. Mechanistically, DHM significantly downregulated the Bcl-2 expression, and upregulated the mRNA and protein levels of Cleaved-Caspase 3, Cleaved- Caspase 9, Bak, Bax and Bad. Furthermore, in the nude mice tumorigenic model, DHM treatment greatly decreased the weight of the HCC tumors compared to the weights in control and NDP group. Conclusions: DHM could suppress cell proliferation, migration, invasion, and facilitated apoptosis in Hep3B cells. These findings could provide novel insights to develop potential therapeutic strategy for the clinical treatment of HCC.

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Dihydromyricetin reverses MRP2-induced multidrug resistance by preventing NF-κB-Nrf2 signaling in colorectal cancer cell

Cited by 39 publications

References 44 publications

The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles

Antitumor Effects of Dihydromyricetin on the Proliferation, Migration and Apoptosis of Human Hepatocellular Carcinoma Hep3B Cells

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