Cyanidin inhibits EMT induced by oxaliplatin<i>via</i>targeting the PDK1–PI3K/Akt signaling pathway

Li, Xiang; Zhang, Zesheng; Zhang, Xiaohan; Yang, Shengnan; Liu, Dong; Diao, Cuiru; Wang, Hao; Zheng, Fangfang

doi:10.1039/c8fo01611a

Cited by 28 publications

(21 citation statements)

References 32 publications

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“…Moreover, Li et al demonstrated that cyanidin could reverse the drug resistance and enhance the efficacy of oxaliplatin on hepatic cellular cancer. Eventually, cyanidin suppressed migration and reversed changes in EMT biomarkers induced by oxaliplatin and increased its sensitivity in hepatic cellular cancer cell lines via PDK1-PI3K/AKT signaling [ 10 ].…”

Section: Targeting Metastatic Cancermentioning

confidence: 99%

“… Classification, food sources, and chemical structure of flavonoids [ 4 , 10 , 34 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. …”

Section: Figurementioning

confidence: 99%

“…The use of current anti-cancer therapeutics is associated with acquired resistance and reoccurrence of the disease with subsequent spread of metastasis and eventual rise in mortality [ 7 , 8 , 9 ]. Flavonoids can effectively improve the efficacy of anti-cancer agents [ 8 , 10 , 11 ]. Therefore, results of the cancer research demonstrating a wide spectrum of anti-cancer effects of flavonoids, mostly in preclinical evaluations, should be necessarily well translated into the clinical cancer treatment research, where there is currently lack of sufficient evidence.…”

Section: Introductionmentioning

confidence: 99%

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Flavonoids in Cancer Metastasis

Líšková

Koklesová

Samec

et al. 2020

Cancers

118

128

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Metastasis represents a serious complication in the treatment of cancer. Flavonoids are plant secondary metabolites exerting various health beneficiary effects. The effects of flavonoids against cancer are associated not only with early stages of the cancer process, but also with cancer progression and spread into distant sites. Flavonoids showed potent anti-cancer effects against various cancer models in vitro and in vivo, mediated via regulation of key signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of epithelial-mesenchymal transition or regulatory molecules such as MMPs, uPA/uPAR, TGF-β and other contributors of the complex process of metastatic spread. Moreover, flavonoids modulated also the expression of genes associated with the progression of cancer and improved inflammatory status, a part of the complex process involved in the development of metastasis. Flavonoids also documented clear potential to improve the anti-cancer effectiveness of conventional chemotherapeutic agents. Most importantly, flavonoids represent environmentally-friendly and cost-effective substances; moreover, a wide spectrum of different flavonoids demonstrated safety and minimal side effects during long-termed administration. In addition, the bioavailability of flavonoids can be improved by their conjugation with metal ions or structural modifications by radiation. In conclusion, anti-cancer effects of flavonoids, targeting all phases of carcinogenesis including metastatic progression, should be implemented into clinical cancer research in order to strengthen their potential use in the future targeted prevention and therapy of cancer in high-risk individuals or patients with aggressive cancer disease with metastatic potential.

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Section: Targeting Metastatic Cancermentioning

confidence: 99%

“… Classification, food sources, and chemical structure of flavonoids [ 4 , 10 , 34 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. …”

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Flavonoids in Cancer Metastasis

Líšková

Koklesová

Samec

et al. 2020

Cancers

118

128

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“…To date, studies of the anticancer mechanisms of anthocyanins have focused on the anthocyanidin aglycone. The reported studies showed that anthocyanidin could affect signalling pathways related to proliferation and apoptosis of tumour cells [10], e.g., inhibiting the proinflammatory NF-κB pathway [11], targeting the PDK1-PI3K/Akt signalling pathway [12], enhancing the expression of p21WAF1 and suppressing the expression of cyclin A/B simultaneously [13].…”

Section: Introductionmentioning

confidence: 99%

Glycosylation of anthocyanins enhances the apoptosis of colon cancer cells by handicapping energy metabolism

Jing

Song

Liu

et al. 2020

BMC Complement Med Ther

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Background While anthocyanins are proven to be effective in inhibiting tumour cell proliferation, the underlying mechanisms remain unclear. This research aims to explore the glycosylation of anthocyanins in the tumour inhibitory effects and the potential mechanism. Methods The tumour inhibitory effect on mouse colon cancer cells (MC38) was examined by MTT and flow cytometric analyses. The inhibitory pathway of anthocyanin was explored by assessment of tumour cell mitochondrial membrane potential (MMP), the caspase-3 and caspase-9 activity, as well as the cell energy metabolism in terms of the glucose uptake, the NAD+/NADH ratio and the ATP level. Results We found that 500 μM bilberry anthocyanins extract (BAE) induced 48.1% mitochondrial damage, activated the downstream caspase cascade to form apoptotic bodies (caspase-3 activity increased by 169%, caspase-9 activity increased by 186%), and inhibited cell proliferation (survival rate: 55.97%, 24 h). In contrast, the same concentration of anthocyanidin (cyanidin) led to marginal mitochondrial damage (only 9.85%) and resulted in little inhibition of MC38 cells (survival rate: 86.84%, 24 h). For cells incubated with 500 μM BAE, reactive oxygen species (ROS) decreased by 53.8%, but the ratio of NAD+/NADH increased to 3.67, demonstrating that the mitochondrial damage was induced by blocking energy metabolism. Furthermore, cell energy metabolism is related to glucose uptake since the presence of 200 μM GLUT1 inhibitor substantially enhanced the inhibitory effects of cyanidin-3-O-glucoside (Cy-3-Glu) at 500 μM (survival rate: 51.08%, 24 h). Conclusions The study suggested that the glycosides of anthocyanins might handicap glucose transport and inhibit energy metabolism, which, in turn, led to mitochondrial damage and apoptosis of tumour cells.

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“…PDK1/PI3K/AKT pathway is a well-known driver of lung cancer progression. The activation of PDK1/PI3K/AKT pathway has also been linked to cancer metastasis and resistance,14,15 making it accountable for the high aggressiveness of cancers. Emerging evidences have shown that several putative miRNAs regulate lung cancer progression through the PDK1/PI3K/AKT pathway 16–18.…”

Section: Introductionmentioning

confidence: 99%

<p>MicroRNA-503 Inhibits Non-Small Cell Lung Cancer Progression By Targeting PDK1/PI3K/AKT Pathway</p>

Wei¹,

Liao²,

Deng³

et al. 2019

OTT

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ObjectivesThe aim of the study was to study the role of dysregulated expression of a microRNA (miRNA), miR-503, in non-small-cell lung cancer (NSCLC) and investigate the underlying mechanism.MethodsQuantitative real-time PCR (qRT-PCR) and in situ hybridization staining (ISH) were used to evaluate the expression level of miR-503 in NSCLC tissues and paired adjacent tissues. CCK-8, colony formation and flow cytometry were performed to explore the effects of miR-503 overexpression on cell proliferation, colony formation and apoptosis. Cells with miR-503 overexpression were used to initiate xenograft models. Dual luciferase reporter assay, qRT-PCR, immunohistochemistry and Western blotting were conducted to investigate the interaction of miR-503 and its potential target.ResultsSignificantly downregulated miR-503 was found in NSCLC tumor tissues and cell lines. miR-503 overexpression significantly inhibited NSCLC cell proliferation, migration and invasion. PDK1 was predicted as the direct targets of miR-503. PDK1 overexpression reversed the inhibitory effects of miR-503 on biological functions, while PDK1 silencing significantly counteracted miR-503 inhibitor-induced pro-tumor effects in A549 cells. Mechanistically, upregulation of miR-503 inhibited PDK1 expression and subsequently caused the inactivation of PI3K/AKT pathway.ConclusionOur results suggest that miR-503 inhibits NSCLC progression by targeting PDK1/PI3K/AKT pathway, potentiating the use of miR-503 as a biomarker and therapeutic target for NSCLC.

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Cyanidin inhibits EMT induced by oxaliplatinviatargeting the PDK1–PI3K/Akt signaling pathway

Abstract: Anthocyanins have been shown to exhibit antitumor activity in several cancers in vitro and in vivo.

Cited by 28 publications

References 32 publications

Flavonoids in Cancer Metastasis

Flavonoids in Cancer Metastasis

Glycosylation of anthocyanins enhances the apoptosis of colon cancer cells by handicapping energy metabolism

<p>MicroRNA-503 Inhibits Non-Small Cell Lung Cancer Progression By Targeting PDK1/PI3K/AKT Pathway</p>

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