Resveratrol enhances the sensitivity of FL118 in triple-negative breast cancer cell lines via suppressing epithelial to mesenchymal transition

Sağlam, Atiye Seda Yar; Kayhan, Handan; Alp, Ebru; Onen, Hacer Ilke

doi:10.1007/s11033-020-06078-y

Cited by 10 publications

(6 citation statements)

References 45 publications

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“…Enhancement of chemotherapy sensitivity in tumor cells using naturally occurring biomolecules is a new and promising strategy aiming to promote the efficacy of conventional chemotherapeutics and targeted drugs [ 69 ]. Several studies suggest that inhibition or reversal of EMT by natural products results in resensitizing drug resistant cancer cells [ 15 , 21 , 22 , 27 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Resveratrol (phytoalexin) is a polyphenol, found in grapes, chocolate, and peanuts [ 20 ]. The regulatory role of resveratrol in EMT, leading to chemosensitization, has also been extensively studied [ 15 , 21 , 22 , 23 ]. Recently, apigenin, a natural flavonoid, was shown to act as an inhibitor of Snail, which is a key regulator of EMT [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines

et al. 2021

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Numerous natural products exhibit antiproliferative activity against cancer cells by modulating various biological pathways. In this study, we investigated the potential use of eight natural compounds (apigenin, curcumin, epigallocatechin gallate, fisetin, forskolin, procyanidin B2, resveratrol, urolithin A) and two repurposed agents (fulvestrant and metformin) as chemotherapy enhancers and mesenchymal-to-epithelial (MET) inducers of cancer cells. Screening of these compounds in various colon, breast, and pancreatic cancer cell lines revealed anti-cancer activity for all compounds, with curcumin being the most effective among these in all cell lines. Although some of the natural products were able to induce MET in some cancer cell lines, the MET induction was not related to increased synergy with either 5-FU, irinotecan, gemcitabine, or gefitinib. When synergy was observed, for example with curcumin and irinotecan, this was unrelated to MET induction, as assessed by changes in E-cadherin and vimentin expression. Our results show that MET induction is compound and cell line specific, and that MET is not necessarily related to enhanced chemosensitivity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines

et al. 2021

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“…Breast cancer -down-expression of mesenchymal markers (Fibronectin 1 and Vimentin) -decreasing the expression of ANGPTL4 and CXCL8 mRNA levels -antagonizing TGF-b signaling by activating SIRT7 deacetylase activity toward SMAD4 degradation (27) -reversing TGF-b1-induced EMT through the PI3K/AKT, Smad, and MMP Pathways (28) -preventing EGF-induced EMT by inhibiting Na+ channel expression (29) -inhibition of EGF-induced EMT by prevention of ERK activation (30) -inhibiting YB-1 phosphorylation induced by LPA and blocking EZH2/amphiregulin signaling axis (31) -inhibiting EMT via induction of Rad9 (32) -promoting the epithelial-type alternative splicing of Cd44, Enah, and FGFR2 pre-mRNAs by upregulating KHSRP and hnRNPA1 expression (33) -promoting sensitization to doxorubicin by inhibiting EMT through modulating SIRT1/b-catenin signaling (34) -overcoming acquired tamoxifen resistance by reversing EMT through suppressing endogenous TGF-b1 production and Smad phosphorylation (35) -reduction of MK-2206(AKT inhibitor)-induced EMT via inducing b-TrCP-mediated Twist1 degradation (36) -enhancing the sensitivity of FL118 in triple-negative breast cancer cell lines through suppression of EMT process (37) Lung cancer -suppression of TGF-b1-induced EMT via decreasing ROS and inhibiting mitochondrial functions (38,39)…”

Section: Disease Condition Main Mechanism Refyearmentioning

confidence: 99%

“…Li et al reported that RES could promote the b-transducin repeat containing protein (b-TrCP)-mediated Twist1 degradation and reduce MK-2206 (AKT inhibitor)induced EMT (36). In addition, Yar et al found that resveratrol could enhance the sensitivity of FL118 in triplenegative breast cancer cell lines by inhibiting EMT (37). It was reported that resveratrol decreased mammary promoter hypermethylation of the tumor suppressor gene Ras association domain family 1a (RASSF-1a) in women at increased risk for breast cancer (155).…”

Section: Non-digestive Cancersmentioning

confidence: 99%

Resveratrol and Its Analogs: Potent Agents to Reverse Epithelial-to-Mesenchymal Transition in Tumors

et al. 2021

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Epithelial-to-mesenchymal transition (EMT), a complicated program through which polarized epithelial cells acquire motile mesothelial traits, is regulated by tumor microenvironment. EMT is involved in tumor progression, invasion and metastasis via reconstructing the cytoskeleton and degrading the tumor basement membrane. Accumulating evidence shows that resveratrol, as a non-flavonoid polyphenol, can reverse EMT and inhibit invasion and migration of human tumors via diverse mechanisms and signaling pathways. In the present review, we will summarize the detailed mechanisms and pathways by which resveratrol and its analogs (e.g. Triacetyl resveratrol, 3,5,4’-Trimethoxystilbene) might regulate the EMT process in cancer cells to better understand their potential as novel anti-tumor agents. Resveratrol can also reverse chemoresistance via EMT inhibition and improvement of the antiproliferative effects of conventional treatments. Therefore, resveratrol and its analogs have the potential to become novel adjunctive agents to inhibit cancer metastasis, which might be partly related to their blocking of the EMT process.

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“…RES induced apoptosis in breast cancer tumor cells by activating apoptosis regulator BAX (Bcl-2-associated X protein) and caspase-3 [18]. RES, alone and in combination with other drugs or natural products, decreased drug resistance and increased the expression of PARP, caspase-3, 8, and 9 in MDA-MB-231 and MDA-MB-436 TNBC cell lines [19][20][21][22][23][24]. Piceatannol, a hydroxylated RES analog, showed PARP activation in human leukemia HL-60 cells [25].…”

Section: Introductionmentioning

confidence: 99%

Arachidin-1, a Prenylated Stilbenoid from Peanut, Induces Apoptosis in Triple-Negative Breast Cancer Cells

Mohammadhosseinpour

Fang

et al. 2022

IJMS

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Triple-negative breast cancer (TNBC) is unresponsive to typical hormonal treatments, causing it to be one of the deadliest forms of breast cancer. Investigating alternative therapies to increase survival rates for this disease is essential. The goal of this study was to assess cytotoxicity and apoptosis mechanisms of prenylated stilbenoids in TNBC cells. The prenylated stilbenoids arachidin-1 (A-1) and arachidin-3 (A-3) are analogs of resveratrol (RES) produced in peanut upon biotic stress. The anticancer activity of A-1 and A-3 isolated from peanut hairy root cultures was determined in TNBC cell lines MDA-MB-231 and MDA-MB-436. After 24 h of treatment, A-1 exhibited higher cytotoxicity than A-3 and RES with approximately 11-fold and six-fold lower IC50, respectively, in MDA-MB-231 cells, and nine-fold and eight-fold lower IC50, respectively, in MDA-MB-436 cells. A-1 did not show significant cytotoxicity in the non-cancerous cell line MCF-10A. While A-1 blocked cell division in G2-M phases in the TNBC cells, it did not affect cell division in MCF-10A cells. Furthermore, A-1 induced caspase-dependent apoptosis through the intrinsic pathway by activating caspase-9 and PARP cleavage, and inhibiting survivin. In conclusion, A-1 merits further research as a potential lead molecule for the treatment of TNBC.

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Resveratrol enhances the sensitivity of FL118 in triple-negative breast cancer cell lines via suppressing epithelial to mesenchymal transition

Cited by 10 publications

References 45 publications

Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines

Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines

Resveratrol and Its Analogs: Potent Agents to Reverse Epithelial-to-Mesenchymal Transition in Tumors

Arachidin-1, a Prenylated Stilbenoid from Peanut, Induces Apoptosis in Triple-Negative Breast Cancer Cells

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