Resveratrol induces chemosensitization to 5-fluorouracil through up-regulation of intercellular junctions, Epithelial-to-mesenchymal transition and apoptosis in colorectal cancer

Buhrmann, Constanze; Shayan, Parviz; Kraehe, Patricia; Popper, Bastian; Goel, Ajay; Shakibaei, Mehdi

doi:10.1016/j.bcp.2015.08.105

Cited by 133 publications

(123 citation statements)

References 78 publications

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“…To date, accumulating evidence indicates that EMT plays an important role in the initiation and development of cancer cells, and some extracellular components surrounding tumor microenvironment exert active effects on EMT 17–19. EGF, a kind of extracellular factor, can be derived from many types of cells within the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

The critical role of EGF-β-catenin signaling in the epithelial-mesenchymal transition in human glioblastoma

Wang

et al. 2017

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To date, β-catenin has been reported to be implicated in mediating the epithelial-mesenchymal transition (EMT) in a variety of human cancers, which can be triggered by EGF. However, the mechanisms underlying EGF-β-catenin pathway-induced EMT of glioblastoma multiforme (GBM) have not been reported previously. In the present study, immunohistochemistry, reverse transcription polymerase chain reaction, and Western blot were applied to investigate the effect of EGF-β-catenin pathway on EMT of GBM. Here, we identified that β-catenin mRNA and protein levels were up-regulated in GBM tissues and four kinds of glioblastoma cell lines, including T98G, A172, U87, and U251 cells, compared with normal brain tissue and astrocytes. In U87 cell line, inhibition of β-catenin by siRNA suppressed EGF-induced proliferation, migration, invasiveness, and the expression of EMT activators (Snail and Slug). In addition, the expression of epithelial markers (E-cadherin) was up-regulated and the expression of mesenchymal markers (N-cadherin and MMP9) was down-regulated. Finally, inhibitor of PI3K/Akt signaling pathways inactivated the EGF-β-catenin-induced EMT. In conclusion, β-catenin-EMT pathway induced by EGF is important for GBM progression by the PI3K/Akt pathways. Inhibition of β-catenin leads to suppression of EGF pathway-induced EMT, which provides a new way to treat GBM patients.

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Section: Discussionmentioning

confidence: 99%

The critical role of EGF-β-catenin signaling in the epithelial-mesenchymal transition in human glioblastoma

Wang

et al. 2017

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“…The animals that received gedunin did not exhibit any discomfort. This is important to measure in order to avoid harsh and severe side effects usually recorded in many of the conventional chemotherapies available today [40]. Furthermore, gedunin inhibited micro–metastasis in the brain, liver and lung when compared to control animals.…”

Section: Discussionmentioning

confidence: 99%

Gedunin inhibits pancreatic cancer by altering sonic hedgehog signaling pathway

et al. 2016

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INTRODUCTIONThe lack of efficient treatment options for pancreatic cancer highlights the critical need for the development of novel and effective chemotherapeutic agents. The medicinal properties found in plants have been used to treat many different illnesses including cancers. This study focuses on the anticancer effects of gedunin, a natural compound isolated from Azadirachta indica.METHODSAnti–proliferative effect of gedunin on pancreatic cancer cells was assessed using MTS assay. We used matrigel invasion assay, scratch assay, and soft agar colony formation assay to measure the anti–metastatic potential of gedunin. Immunoblotting was performed to analyze the effect of gedunin on the expression of key proteins involved in pancreatic cancer growth and metastasis. Gedunin induced apoptosis was measured using flow cytometric analysis. To further validate, xenograft studies with HPAC cells were performed.RESULTSGedunin treatment is highly effective in inducing death of pancreatic cancer cells via intrinsic and extrinsic mediated apoptosis. Our data further indicates that gedunin inhibited metastasis of pancreatic cancer cells by decreasing their EMT, invasive, migratory and colony formation capabilities. Gedunin treatment also inhibited sonic hedgehog signaling pathways. Further, experiments with recombinant sonic hedgehog protein and Gli inhibitor (Gant-61) demonstrated that gedunin induces its anti–metastatic effect through inhibition of sonic hedgehog signaling. The anti–cancer effect of gedunin was further validated using xenograft mouse model.CONCLUSIONOverall, our data suggests that gedunin could serve as a potent anticancer agent against pancreatic cancers.

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“…The combination of drugs resulted in cell cycle arrest and inhibition of the p38 MAPK pathway [40]. Curcumin and another antioxidant, resveratrol, have been shown to enhance sensitivity of colorectal cancer cells to 5-fluoruracil by inhibiting the NF-κB pathway [41, 42]. …”

Section: Discussionmentioning

confidence: 99%

MnTnBuOE-2-PyP protects normal colorectal fibroblasts from radiation damage and simultaneously enhances radio/chemotherapeutic killing of colorectal cancer cells

et al. 2016

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Manganese porphyrins have been shown to be potent radioprotectors in a variety of cancer models. However, the mechanism as to how these porphyrins protect normal tissues from radiation damage still remains largely unknown. In the current study, we determine the effects of the manganese porphyrin, MnTnBuOE-2-PyP, on primary colorectal fibroblasts exposed to irradiation. We found that 2 Gy of radiation enhances the fibroblasts' ability to contract a collagen matrix, increases cell size and promotes cellular senesence. Treating fibroblasts with MnTnBuOE-2-PyP significantly inhibited radiation-induced collagen contraction, preserved cell morphology and also inhibited cellular senescence. We further showed that MnTnBuOE-2-PyP enhanced the overall viability of the fibroblasts following exposure to radiation but did not protect colorectal cancer cell viability. Specifically, MnTnBuOE-2-PyP in combination with irradiation, caused a significant decrease in tumor clonogenicity. Since locally advanced rectal cancers are treated with chemoradiation therapy followed by surgery and non-metastatic anal cancers are treated with chemoradiation therapy, we also investigated the effects of MnTnBuOE-2-PyP in combination with radiation, 5-fluorouracil with and without Mitomycin C. We found that MnTnBuOE-2-PyP in combination with Mitomycin C or 5-fluorouracil further enhances those compounds' ability to suppress tumor cell growth. When MnTnBuOE-2-PyP was combined with the two chemotherapeutics and radiation, we observed the greatest reduction in tumor cell growth. Therefore, these studies indicate that MnTnBuOE-2-PyP could be used as a potent radioprotector for normal tissue, while at the same time enhancing radiation and chemotherapy treatment for rectal and anal cancers.

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Resveratrol induces chemosensitization to 5-fluorouracil through up-regulation of intercellular junctions, Epithelial-to-mesenchymal transition and apoptosis in colorectal cancer

Cited by 133 publications

References 78 publications

The critical role of EGF-β-catenin signaling in the epithelial-mesenchymal transition in human glioblastoma

The critical role of EGF-β-catenin signaling in the epithelial-mesenchymal transition in human glioblastoma

Gedunin inhibits pancreatic cancer by altering sonic hedgehog signaling pathway

MnTnBuOE-2-PyP protects normal colorectal fibroblasts from radiation damage and simultaneously enhances radio/chemotherapeutic killing of colorectal cancer cells

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Resveratrol induces chemosensitization to 5-fluorouracil through up-regulation of intercellular junctions, Epithelial-to-mesenchymal transition and apoptosis in colorectal cancer

Cited by 133 publications

References 78 publications

The critical role of EGF-&beta;-catenin signaling in the epithelial-mesenchymal transition in human glioblastoma

The critical role of EGF-&beta;-catenin signaling in the epithelial-mesenchymal transition in human glioblastoma

Gedunin inhibits pancreatic cancer by altering sonic hedgehog signaling pathway

MnTnBuOE-2-PyP protects normal colorectal fibroblasts from radiation damage and simultaneously enhances radio/chemotherapeutic killing of colorectal cancer cells

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The critical role of EGF-β-catenin signaling in the epithelial-mesenchymal transition in human glioblastoma

The critical role of EGF-β-catenin signaling in the epithelial-mesenchymal transition in human glioblastoma