Role of Reactive Oxygen Intermediates in Cellular Responses to Dietary Cancer Chemopreventive Agents

Antosiewicz, Jędrzej; Ziółkowski, Wiesław; Kar, Siddhartha; Powolny, Anna A.; Singh, Shivendra V.

doi:10.1055/s-2008-1081307

Cited by 97 publications

(78 citation statements)

References 100 publications

(189 reference statements)

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“…ROS generation plays an important role in cell proliferation as well as in apoptosis, and it triggers signal transduction, culminating in cell cycle arrest and ultimately cell death (Antosiewicz et al, 2008). ROS generation has been reported to be associated with curcumin-induced apoptosis in many cancer cells.…”

Section: Curcumin Induces Oxidative-stress Apoptosismentioning

confidence: 99%

Curcumin Induces Apoptosis in Human Colorectal Carcinoma (HCT-15) Cells by Regulating Expression of Prp4 and p53

Shehzad

Lee

Huh

et al. 2013

Molecules and Cells

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Curcumin (diferuloylmethane), the yellow pigment of turmeric, is one of the most commonly used and extensively studied phytochemicals due to its pleiotropic effects in several human cancers. In the current study, the therapeutic efficacy of curcumin was investigated in human colorectal carcinoma HCT-15 cells. Curcumin inhibited HCT-15 cells proliferation and induced apoptosis in a dose-and time-dependent manner. Hoechst 33342 and DCFHDA staining revealed morphological and biochemical features of apoptosis as well as ROS generation in HCT-15 cells treated with 30 and 50 µM curcumin. Over-expression of pre-mRNA processing factor 4B (Prp4B) and p53 mutations have been reported as hallmarks of cancer cells. Western blot analysis revealed that curcumin treatment activated caspase-3 and decreased expression of p53 and Prp4B in a time-dependent manner. Transfection of HCT-15 cells with Prp4B clone perturbed the growth inhibition induced by 30 µM curcumin. Fractionation of cells revealed increased accumulation of Prp4B in the nucleus, following its translocation from the cytoplasm. To further evaluate the underlying mechanism and survival effect of Prp4B, we generated siRNA-Prp4B HCT15 clones. Knockdown of Prp4B with siRNA diminished the protective effects of Prp4B against curcumin-induced apoptosis. These results suggest a possible underlying molecular mechanism in which Prp4B over-expression and activity are closely associated with the survival and regulation of apoptotic events in human colon cancer HCT-15 cells.

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Section: Curcumin Induces Oxidative-stress Apoptosismentioning

confidence: 99%

Curcumin Induces Apoptosis in Human Colorectal Carcinoma (HCT-15) Cells by Regulating Expression of Prp4 and p53

Shehzad

Lee

Huh

et al. 2013

Molecules and Cells

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“…Cytotoxicity has been shown to rely on the modulation of different cell cycle regulators causing a G 2 M arrest and on the induction of intrinsic and extrinsic apoptotic cell death (8). Additionally, the generation of reactive oxygen species Autophagy and cell death signaling following dietary sulforaphane act independently of each other and require oxidative stress in pancreatic cancer (ROS) by SFN has been identified as playing a crucial role in triggering apoptosis (9). Furthermore, enhanced autophagy has been reported in prostate cancer cells in response to cellular stress of SFN-induced ROS generation, apoptosis induction and damaged mitochondria and endoplasmatic reticulum (10,11).…”

Section: Introductionmentioning

confidence: 99%

Autophagy and cell death signaling following dietary sulforaphane act independently of each other and require oxidative stress in pancreatic cancer

Naumann

Fortunato

Zentgraf³

et al. 2011

Int J Oncol

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Abstract. the broccoli isothiocyanate, sulforaphane (Sfn), was recently identified as being capable of eliminating highly therapy-resistant pancreatic carcinoma (PC) cells without inducing toxic side effects. While SFN has been shown to stimulate autophagy or 'self-eating', it is unclear whether this catabolic process is a pro-or anti-tumorigenic response. To investigate the role of autophagy in SFN-induced cell death, established PC cell lines were treated with SFN, and the induction of autophagy was evaluated by detecting the abundance of autophagic vesicles by electron microscopy, the increase in converted LC3-II by Western blot analysis and the autophagosome puncta of GFP-LC3 by immunofluorescence. SFN-induced autophagy was suppressed by the autophagy inhibitor chloroquine, while the autophagy inducer rapamycin did not further enhance autophagy in PC cells. Importantly, neither modulator altered SFN cytotoxicity, suggesting that SFN-induced autophagy and cell death act independently of each other. In contrast, the antioxidant N-acetyl-cysteine sustained cell viability and prevented autophagy induction after SFN exposure, indicating that both signaling pathways depend on reactive oxygen species (ROS). Our studies provide a valuable new mechanistic insight into the SFN-induced elimination of PC cells and suggest that an SFN-enriched diet potentially enhances ROS-releasing chemotherapeutic agents.

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“…PEITC can induce cell cycle arrest and apoptotic cell death in various tumor types (6)(7)(8)(9)(10)(11)(12). In our previous study, PEITC induced apoptosis through the extrinsic (death receptor) and intrinsic (mitochondrial) pathways, dysfunction of mitochondria and ROS-induced ER stress in GBM 8401 cells (13).…”

Section: Introductionmentioning

confidence: 99%

PEITC inhibits human brain glioblastoma GBM 8401 cell migration and invasion through the inhibition of uPA, Rho A, and Ras with inhibition of MMP-2, -7 and -9 gene expression

et al. 2015

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Abstract. Glioblastoma is the most aggressive primary brain malignancy, and the efficacy of multimodality treatments remains unsatisfactory. Phenethyl isothiocyanate (PEITC), one member of the isothiocyanate family, was found to inhibit the migration and invasion of many types of human cancer cells. In our previous study, PEITC induced the apoptosis of human brain glioblastoma GBM 8401 cells through the extrinsic and intrinsic signaling pathways. In the present study, we first investigated the effects of PEITC on the migration and invasion of GBM 8401 cells. PEITC decreased the migration of GBM 8401 cells in a dose-dependent manner as determined from scratch wound healing and Transwell migration assays. The percentage of inhibition ranged from 46.89 to 15.75%, and from 27.80 to 7.31% after a 48-h treatment of PEITC as determined from the Transwell migration assay and invasion assay, respectively. The western blot analysis indicated that PEITC decreased the levels of proteins associated with migration and invasion, Ras, uPA, RhoA, GRB2, p-p38, p-JNK, p-ERK, p65, SOS1, MMP-2, MMP-9 and MMP-13, in a dose-dependent manner. Real-time PCR analyses revealed that PEITC reduced the mRNA levels of MMP-2, MMP-7, MMP-9 and RhoA in a dose-and time-dependent manner. PEITC exhibited potent anticancer activities through the inhibition of migration and invasion in the GBM 8401 cells. Our findings elucidate the possible molecular mechanisms and signaling pathways of the anti-metastatic effects of PEITC on human brain glioblastoma cells, and PEITC may be considered as a therapeutic agent. IntroductionGlioblastoma is the most aggressive primary brain malignancy with a median survival rate of 14.6 months from diagnosis in unselected patients, even following maximal, feasible surgical resection, radiotherapy and standard adjuvant temozolomide (TMZ) therapy (1). Only 0.4-0.5% of all GBM patients with extracranial metastasis has been reported, which may be attributable to the extremely shortened survival of these patients (2). Combining radiotherapy and TMZ provides better survival outcomes of glioblastoma patients than radiotherapy alone (3). Survival and recurrence are significantly associated with the extent of resection and residual volume (4). Gross total resection associated with survival improvement is not always possible as the preservation of neurological functions is necessary. The efficacy of current multimodality treatments including surgery, radiotherapy, chemotherapy for this tumor remains unsatisfactory.Phenethyl isothiocyanate (PEITC) is one of the most extensively studied isothiocyanates (5). PEITC can induce cell cycle arrest and apoptotic cell death in various tumor types (6-12). In our previous study, PEITC induced apoptosis through the extrinsic (death receptor) and intrinsic (mitochondrial) pathways, dysfunction of mitochondria and ROS-induced ER stress in GBM 8401 cells (13). PEITC displayed anti-metastatic PEITC inhibits human brain glioblastoma GBM 8401 cell migration and invasion through the inhibition of uPA,...

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Role of Reactive Oxygen Intermediates in Cellular Responses to Dietary Cancer Chemopreventive Agents

Cited by 97 publications

References 100 publications

Curcumin Induces Apoptosis in Human Colorectal Carcinoma (HCT-15) Cells by Regulating Expression of Prp4 and p53

Curcumin Induces Apoptosis in Human Colorectal Carcinoma (HCT-15) Cells by Regulating Expression of Prp4 and p53

Autophagy and cell death signaling following dietary sulforaphane act independently of each other and require oxidative stress in pancreatic cancer

PEITC inhibits human brain glioblastoma GBM 8401 cell migration and invasion through the inhibition of uPA, Rho A, and Ras with inhibition of MMP-2, -7 and -9 gene expression

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