Resveratrol and curcumin synergistically induces apoptosis in cigarette smoke condensate transformed breast epithelial cells through a p21Waf1/Cip1 mediated inhibition of Hh-Gli signaling

Mohapatra, Purusottam; Satapathy, Shakti Ranjan; Siddharth, Sumit; Das, Diptikanta; Nayak, Anmada; Kundu, Chanakya Nath

doi:10.1016/j.biocel.2015.07.009

Cited by 40 publications

(17 citation statements)

References 45 publications

(58 reference statements)

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“…Slusarz et al (29) reported that curcumin caused major reductions in GLI1 mRNA concentrations in transgenic prostate carcinoma mice. A recent study also revealed that resveratrol and curcumin synergistically caused apoptosis in cigarette smoke induced breast cancer cells through p21 (Waf/Cip1) mediated inhibition of Hedgehog-GLI cascade (30). In the present study, we showed that curcumin remarkably inhibited hypoxia-mediated activation of Hh signaling pathway.…”

Section: Discussionsupporting

confidence: 68%

Curcumin inhibits hypoxia-induced epithelial-mesenchymal transition in pancreatic cancer cells via suppression of the hedgehog signaling pathway

et al. 2016

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Abstract. Hypoxic microenvironment, a common feature of pancreatic cancer, is associated with tumor proliferation, metastasis and epithelial-mesenchymal transition (EMT) changes. In recent years, many natural agents, including curcumin, have been proven to possess the ability to inhibit the progression of pancreatic cancer. However, whether curcumin is able to suppress hypoxia-induced pancreatic cancer progression and the underlying mechanisms are still not fully elucidated. The aim of the present study was to evaluate whether curcumin affects hypoxia-induced EMT and the activation of Hh signaling pathway in pancreatic cancer. The human pancreatic cancer cell line Panc-1, was treated with hypoxic condition and curcumin. Cell proliferation was assessed by the MTT assay. Wound healing assay and Transwell invasion assay were used to detect the migratory and invasive activity of cancer cells. The EMT-related factors, E-cadherin, N-cadherin, vimentin were detected by QT-PCR, western blot analysis and immunofluorescence staining. The Hh signaling-related factors, SHH, SMO and GLI1 were detected by western blot analysis. The results of present study showed that curcumin could not only inhibit the hypoxia-induced cell proliferation, migration and invasion in pancreatic cancer, but also mediate the expression of EMT-related factors. In addition, curcumin remarkably inhibited hypoxia-mediated activation of Hh signaling pathway. Taken together, these data indicate that curcumin plays an important role in suppressing hypoxiainduced pancreatic cancer metastasis by inhibiting the Hh signaling pathway. Curcumin might be a potential candidate for chemoprevention of this severe disease. IntroductionPancreatic cancer is one of the most aggressive malignant diseases with a median survival time of less than 6 months and a 5-year survival rate of <5% (1). In 2015, it was estimated that 48,960 subjects will be newly diagnosed with pancreatic cancer and will account for 40,560 cancer-related deaths in the United States (1). Surgical resection remains the only way to cure this severe disease, however, due to the high metastatic rate, the majority of patients are diagnosed at an advanced inoperable stage, and less than 20% of patients are amenable for surgery (2). Even those patients with seemingly resectable pancreatic tumor are not always cured by surgery due to the microscopic systemic spread of cancer cells before the operation intervention (3). Currently, there are very limited therapeutic options for pancreatic cancer, therefore, more constructive and effective interventions for targeting cancer metastasis are urgently needed.Hypoxia (low oxygen tension) is commonly found in solid tumors more than a few millimeters in size and is associated with a poor prognosis (4,5). Tumor hypoxia is strongly associated with enhanced tumor invasiveness, angiogenesis and distant metastasis (4). Hypoxia-inducible factor-1 (HIF-1), which belongs to the basic helix-loop-helix-periodic acidSchiff domain transcription factor family, is a key mediator ...

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Section: Discussionsupporting

confidence: 68%

Curcumin inhibits hypoxia-induced epithelial-mesenchymal transition in pancreatic cancer cells via suppression of the hedgehog signaling pathway

et al. 2016

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“…Among nutraceuticals, curcumin (CUR), the active component of Curcuma longa with anti-inflammatory, antioxidant, and anticancer properties [20–24], has been tested as a potential therapeutic agent in different pathological conditions, including cardiovascular diseases [25–30]. This natural compound has been shown to reduce the production of proatherogenic cytokines in activated human monocytes [31].…”

Section: Introductionmentioning

confidence: 99%

The Nutraceutical Dehydrozingerone and Its Dimer Counteract Inflammation‐ and Oxidative Stress‐Induced Dysfunction of In Vitro Cultured Human Endothelial Cells: A Novel Perspective for the Prevention and Therapy of Atherosclerosis

Profumo

Buttari

D’Arcangelo

et al. 2016

Oxidative Medicine and Cellular Longevity

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Atherosclerosis is characterized by endothelial dysfunction, mainly induced by inflammation and oxidative stress. Increased reactive oxygen species (ROS) production together with increased adhesion molecules and thrombogenic tissue factor (TF) expression on endothelial cells has a key role in proatherogenic mechanisms. Therefore downmodulation of these molecules could be useful for reducing the severity of inflammation and atherosclerosis progression. Dehydrozingerone (DHZ) is a nutraceutical compound with anti-inflammatory and antioxidant activities. In this study we evaluated the ability of DHZ and its symmetric dimer to modulate hydrogen peroxide- (H2O2-) induced ROS production in human umbilical vein endothelial cells (HUVEC). We also evaluated intercellular adhesion molecule- (ICAM-) 1, vascular cell adhesion molecule- (VCAM-) 1, and TF expression in HUVEC activated by tumor necrosis factor- (TNF-) α. HUVEC pretreatment with DHZ and DHZ dimer reduced H2O2-induced ROS production and inhibited adhesion molecule expression and secretion. Of note, only DHZ dimer was able to reduce TF expression. DHZ effects were in part mediated by the inhibition of the nuclear factor- (NF-) κB activation. Overall, our findings demonstrate that the DHZ dimer exerts a potent anti-inflammatory, antioxidant, and antithrombotic activity on endothelial cells and suggest potential usefulness of this compound to contrast the pathogenic mechanisms involved in atherosclerosis progression.

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“…Combination of these drugs resulted in apoptosis in cigarate smoke condensate transformed breast cancer epithelial cells. 12 This article aims to compare the molecular activity of curcumin and resveratrol on certain breast cancer receptors, as an in vitro study to explore the combined use of curcumin, resveratrol in breast cancer treatment.…”

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confidence: 99%

Comparative Insilico Docking Analysis of Curcumin and Resveratrol on Breast Cancer Proteins and their Synergistic Effect on MCF-7 Cell Line

Pushpalatha¹,

Selvamuthukumar²,

Kilimozhi³

2017

JYP

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Object:To compare the molecular activity of curcumin and resveratrol on selected breast cancer protein receptors and to investigate their combination for synergism against human breast cancer MCF-7 cell line. Method: Curcumin and resveratrol were subjected to insilico docking studies using glide to investigate the drug activity against HER2, human oestrogen receptor, ERBB2, epidermal growth factor tyrosine protein kinase C-SRC, and HSP90 proteins. MTT assay was used to assess cell viability of curcumin and resveratrol individually and in combination at 1:1,1:3 and 3:1 ratio respectively. Results: The insilico study revealed good glide score and glide energy for these drugs against breast cancer protein. Curcumin and resveratrol has more binding affinity for proteins with varying amino acid interaction sites. IC 50 for curcumin and resveratrol was observed to be 21.29 and 38.30 µg/ml respectively. IC 50 for the combined treatment with curcumin and resveratrol at the ratio of 1:1,1:3 and 3:1 were observed to be 28.06, 15.20 and 8.29 µg/ml respectively. Combined treatment of curcumin and resveratrol at equal ratio exhibited additive effects while at the ratio of 1:3 and 3:1 exhibited a strong synergistic effect on the cytotoxicity of MCF-7 cell line. Conclusion: Insilico docking analysis helped in identifying and organizing the structural similarity/diversity at the molecular level activity of curcumin and resveratrol. In vitro cell line study provides an insight into the potential application of curcumin and resveratrol codelivery for the chemoprevention and treatment of breast cancer.Key words: Combinatorial effect, Curcumin, Resveratrol, Human breast cancer MCF -7 cells, Insilico anticancer screening, Synergism. Key Message: Synergistic effect of curcumin and resveratrol on breast cancer observed.

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Resveratrol and curcumin synergistically induces apoptosis in cigarette smoke condensate transformed breast epithelial cells through a p21Waf1/Cip1 mediated inhibition of Hh-Gli signaling

Cited by 40 publications

References 45 publications

Curcumin inhibits hypoxia-induced epithelial-mesenchymal transition in pancreatic cancer cells via suppression of the hedgehog signaling pathway

Curcumin inhibits hypoxia-induced epithelial-mesenchymal transition in pancreatic cancer cells via suppression of the hedgehog signaling pathway

The Nutraceutical Dehydrozingerone and Its Dimer Counteract Inflammation‐ and Oxidative Stress‐Induced Dysfunction of In Vitro Cultured Human Endothelial Cells: A Novel Perspective for the Prevention and Therapy of Atherosclerosis

Comparative Insilico Docking Analysis of Curcumin and Resveratrol on Breast Cancer Proteins and their Synergistic Effect on MCF-7 Cell Line

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