Comparison of the anti-cancer effect of Disulfiram and 5-Aza-CdR on pancreatic cancer cell line PANC-1

Dastjerdi, Mehdi Nikbakht; Babazadeh, Zahra; Salehi, Masoud; Hashemibeni, Batool; Kazemi, Mohammad

doi:10.4103/2277-9175.137866

Cited by 12 publications

(8 citation statements)

References 42 publications

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“…Pancreatic cancer is the only major cancer with a 5-year survival rate of less than 6%, indicating that it is one of the deadliest cancers 4 . Since a high proportion of cancers are diagnosed at late-stages, only 10–20% of pancreatic cancer patients are suitable for surgical resection of the cancer 5 6 . With no effective treatments currently available, there is an immediate need for the development of novel therapeutic agents.…”

mentioning

confidence: 99%

Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition

Subramani

Gonzalez

Arumugam

et al. 2016

Sci Rep

131

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The mortality and morbidity rates of pancreatic cancer are high because of its extremely invasive and metastatic nature. Its lack of symptoms, late diagnosis and chemo–resistance and the ineffective treatment modalities warrant the development of new chemo–therapeutic agents for pancreatic cancer. Agents from medicinal plants have demonstrated therapeutic benefits in various human cancers. Nimbolide, an active molecule isolated from Azadirachta indica, has been reported to exhibit several medicinal properties. This study assessed the anticancer properties of nimbolide against pancreatic cancer. Our data reveal that nimbolide induces excessive generation of reactive oxygen species (ROS), thereby regulating both apoptosis and autophagy in pancreatic cancer cells. Experiments with the autophagy inhibitors 3-methyladenine and chloroquine diphosphate salt and the apoptosis inhibitor z-VAD-fmk demonstrated that nimbolide-mediated ROS generation inhibited proliferation (through reduced PI3K/AKT/mTOR and ERK signaling) and metastasis (through decreased EMT, invasion, migration and colony forming abilities) via mitochondrial-mediated apoptotic cell death but not via autophagy. In vivo experiments also demonstrated that nimbolide was effective in inhibiting pancreatic cancer growth and metastasis. Overall, our data suggest that nimbolide can serve as a potential chemo–therapeutic agent for pancreatic cancer.

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mentioning

confidence: 99%

Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition

Subramani

Gonzalez

Arumugam

et al. 2016

Sci Rep

131

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“…Comparable results were achieved on an oral squamous cell line treated with 5-aza-cdR, which in this case produced a significant increase in expression of TSC genes (Chakraborty et al, 2008). 5-Aza-CdR has been approved by FDA for disease treatment through affecting genes directly or indirectly (Yang et al, 2010;Dastjerdi et al, 2014) 0.5-aza-cdR have been used in a clinical setting in myelodysplastic syndrome (Abou Zahr et al, 2015), Therefore, it implied that 5-Aza-CdR may be used as a potential clinical treatment medicine for ischemia/hypoxia brain damage through up-regulation TSC/down-regulation mTOR. Thus, it is conceivable in light of our work on the modulation of DNMTs by hypoxic preconditioning that ischemic/hypoxic conditions may induce DNMTs to alter DNA methylation rates at the hamartin gene, modulating its expression to promote the neuroprotective effect called for under these circumstances (Figure 2).…”

Section: Modulation Of Hamartin Expression By Dna Methylationmentioning

confidence: 88%

Hamartin: An Endogenous Neuroprotective Molecule Induced by Hypoxic Preconditioning

Ren

Stone

et al. 2020

Front. Genet.

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Hypoxic/ischemic preconditioning (HPC/IPC) is an innate neuroprotective mechanism in which a number of endogenous molecules are known to be involved. Tuberous sclerosis complex 1 (TSC1), also known as hamartin, is thought to be one such molecule. It is also known that hamartin is involved as a target in the rapamycin (mTOR) signaling pathway, which functions to integrate a variety of environmental triggers in order to exert control over cellular metabolism and homeostasis. Understanding the role of hamartin in ischemic/hypoxic neuroprotection will provide a novel target for the treatment of hypoxic-ischemic disease. Therefore, the proposed molecular mechanisms of this neuroprotective role and its preconditions are reviewed in this paper, with emphases on the mTOR pathway and the relationship between the expression of hamartin and DNA methylation.

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“…The human breast cancer cell lines, MDA-MB-231 and SK-BR-3 cells, and human pancreatic cancer cell line, Panc1, were supplied by American Type Culture Collection—ATCC (Manassas, VA, USA) and cultured in DMEM containing 10% FBS and 1% antibiotic–antimycotic (final concentrations of 100 U/mL penicillin and 100 μg/mL streptomycin) in an incubator at 37 °C with 5% CO 2 until 75–80% confluency, as described in previous studies [ 61 , 66 , 67 ].…”

Section: Methodsmentioning

confidence: 99%

Involvement of the ERK/HIF-1α/EMT Pathway in XCL1-Induced Migration of MDA-MB-231 and SK-BR-3 Breast Cancer Cells

Thu

Cho

2020

IJMS

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Chemokine–receptor interactions play multiple roles in cancer progression. It was reported that the overexpression of X-C motif chemokine receptor 1 (XCR1), a specific receptor for chemokine X-C motif chemokine ligand 1 (XCL1), stimulates the migration of MDA-MB-231 triple-negative breast cancer cells. However, the exact mechanisms of this process remain to be elucidated. Our study found that XCL1 treatment markedly enhanced MDA-MB-231 cell migration. Additionally, XCL1 treatment enhanced epithelial–mesenchymal transition (EMT) of MDA-MB-231 cells via E-cadherin downregulation and upregulation of N-cadherin and vimentin as well as increases in β-catenin nucleus translocation. Furthermore, XCL1 enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Notably, the effects of XCL1 on cell migration and intracellular signaling were negated by knockdown of XCR1 using siRNA, confirming XCR1-mediated actions. Treating MDA-MB-231 cells with U0126, a specific mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, blocked XCL1-induced HIF-1α accumulation and cell migration. The effect of XCL1 on cell migration was also evaluated in ER-/HER2+ SK-BR-3 cells. XCL1 also promoted cell migration, EMT induction, HIF-1α accumulation, and ERK phosphorylation in SK-BR-3 cells. While XCL1 did not exhibit any significant impact on the matrix metalloproteinase (MMP)-2 and -9 expressions in MDA-MB-231 cells, it increased the expression of these enzymes in SK-BR-3 cells. Collectively, our results demonstrate that activation of the ERK/HIF-1α/EMT pathway is involved in the XCL1-induced migration of both MDA-MB-231 and SK-BR-3 breast cancer cells. Based on our findings, the XCL1–XCR1 interaction and its associated signaling molecules may serve as specific targets for the prevention of breast cancer cell migration and metastasis.

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Comparison of the anti-cancer effect of Disulfiram and 5-Aza-CdR on pancreatic cancer cell line PANC-1

Cited by 12 publications

References 42 publications

Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition

Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition

Hamartin: An Endogenous Neuroprotective Molecule Induced by Hypoxic Preconditioning

Involvement of the ERK/HIF-1α/EMT Pathway in XCL1-Induced Migration of MDA-MB-231 and SK-BR-3 Breast Cancer Cells

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