Caspase-2 Triggers Bax-Bak-dependent and -independent Cell Death in Colon Cancer Cells Treated with Resveratrol

Morser, John; Gandhi, Alankaram Arul; Bhavya, B. C.; Rashmi, Ramachandran; Karunagaran, Devarajan; Indu, Ramachandran; Santhoshkumar, T.R.

doi:10.1074/jbc.m602641200

Cited by 69 publications

(43 citation statements)

References 51 publications

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“…The link between these 2 pathways is mediated by the truncated proapoptotic protein Bid (6). Caspase-2 like caspase-8 is also known to cleave Bid to t-Bid that alters MMP (25). We observed truncation of Bid, mitochondrial hyperpolarization, cytochrome c release, caspase-9 activation followed by caspase-3 activation, and ultimately cleavage of PARP in curcumin-treated HuT-78 cells.…”

Section: Discussionmentioning

confidence: 60%

Oxidative Stress Induced by Curcumin Promotes the Death of Cutaneous T-cell Lymphoma (HuT-78) by Disrupting the Function of Several Molecular Targets

Khan

Gahlot

Majumdar

2012

Molecular Cancer Therapeutics

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Curcumin is known to exert its anticancer effect either by scavenging or by generating reactive oxygen species (ROS). In this study, we report that curcumin-mediated rapid generation of ROS induces apoptosis by modulating different cell survival and cell death pathways in HuT-78 cells. Curcumin induces the activation of caspase-8, -2, and -9, alteration of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-3 and concomitant PARP cleavage, but the addition of caspase inhibitors only partially blocked the curcumin-mediated apoptosis. Curcumin also downregulates the expression of antiapoptotic proteins c-FLIP, Bcl-xL, cellular inhibitor of apoptosis protein, and X-linked IAP in a ROS-dependent manner. Curcumin disrupts the integrity of IKK and beclin-1 by degrading Hsp90. Degradation of IKK leads to the inhibition of constitutive NF-kB. Degradation of beclin-1 by curcumin leads to the accumulation of autophagy-specific marker, microtubule-associated protein-I light chain 3 (LC3), LC3-I. Our findings indicate that HuT-78 cells are vulnerable to oxidative stress induced by curcumin and as a result eventually undergo cell death. Mol Cancer Ther; 11(9); 1873-83. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 60%

Oxidative Stress Induced by Curcumin Promotes the Death of Cutaneous T-cell Lymphoma (HuT-78) by Disrupting the Function of Several Molecular Targets

Khan

Gahlot

Majumdar

2012

Molecular Cancer Therapeutics

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“…Several researchers have reported the activation of the mitochondrial pathway, and therefore caspase-9, by quercetin in leukemia [47] and colon cancer cells [42]. In colon cancer cells, caspase-9 was also cleaved by other polyphenols such as resveratrol [48].…”

Section: Discussionmentioning

confidence: 99%

Role of Bax in quercetin-induced apoptosis in human prostate cancer cells

Lee

Szczepański

Lee

2008

Biochemical Pharmacology

113

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The aim of this study was to investigate the effect of quercetin, a flavonoid, on the apoptotic pathway in a human prostate cell line (LNCaP). We observed that treatment of cells for 24 h with quercetin induced cell death in a dose-dependent manner. A sustained inhibition of the major survival signal, Akt, occurred in quercetin-treated cells. Treatment of LNCaP cells with an apoptosis inducing concentration of quercetin (100 μM) resulted in a rapid decrease in the inhibitory Ser( 473 ) phosphorylation of Akt leading to inhibition of its kinase activity. Quercetin treatment (100 μM) also caused a decrease in Ser( 136 ) phosphorylation of Bad, which is a downstream target of Akt. Protein interaction assay revealed that during treatment with quercetin, Bcl-xL dissociated from Bax and then associated with Bad. Our results also show that quercetin decreases the Bcl-xL:Bax ratio and increases translocation and multimerization of Bax to the mitochondrial membrane. The translocation is accompanied by cytochrome c release, and procaspases-3, -8 and -9 cleavage and increased poly (ADP-ribose) polymerase (PARP) cleavage. Similar results were observed in human colon cancer HCT116Bax +/+ cell line, but not HCT116Bax −/− cell line. Interestingly, at similar concentrations (100 μM), quercetin treatment did not affect the viability or rate of apoptosis in normal human prostate epithelial cell line (PrEC) and rat prostate epithelial cell line (YPEN-1). Our results indicate that the apoptotic processes caused by quercetin are mediated by the dissociation of Bax from Bcl-xL and the activation of caspase families in human prostate cancer cells.

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“…Particularly, by acting as antioxidant, anti-mutagen as well as by inducing phase II drug-metabolizing enzymes, trans-resveratrol inhibits the initiation phase of tumorigenesis; concomitantly, it mediates the anti-inflammatory response and induces cell differentiation, thereby inhibiting tumor promotion and progression, respectively [28]. Subsequently, other groups reported the anti-proliferative and pro-apoptotic activity of trans-resveratrol in several tumor cell lines [2,27,41,56], suggesting that it can function by modulating and interacting with a broad range of cellular targets, ranging from cell surface receptors [5,7] to caspases [43]; from mitochondria [8] and mitochondria-associated proteins [43,50,60], to intracellular protein kinases, such as protein kinase B (PKB)/Akt, PKC, MAP kinases [34,57,58,62,65] and transcription factors (e.g. p53, pRb, c-Jun and NF-jB) [30,37,45,59].…”

Section: Introductionmentioning

confidence: 99%

trans-Resveratrol induces apoptosis in human breast cancer cells MCF-7 by the activation of MAP kinases pathways

et al. 2007

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Polyphenols represent a large class of plantderived molecules with a general chemical structure that act as potent free radical scavengers. They have long been recognized to possess several therapeutic activities ranging from anti-thrombotic to antioxidant. Moreover, the capability of polyphenols to act as reducing or oxidizing molecules depends on the presence of environmental metals and on the concentrations used. In this work we demonstrated that the stilbene trans-resveratrol was able to commit human breast cancer MCF-7 cells to apoptosis. Mainly, we evidenced a pivotal role of the mitochondria in this phenomenon as cytochrome c release into the cytosol was found after the treatment. We further showed that trans-resveratrol was able to affect cellular redox state. In particular, it induced an early production of ROS and lipid oxidation, and only later compromised the GSH/GSSG ratio. This mode of action was mirrored by a temporally different activation of JNK and p38 MAPK , with the former rapidly induced and the latter weakly activated at long intervals. The results obtained demonstrate a pro-apoptotic activity for trans-resveratrol, and suggest a preferential activation of different classes of MAP kinases in response to different oxidative stimuli (ROS versus GSH/GSSG alteration).

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Caspase-2 Triggers Bax-Bak-dependent and -independent Cell Death in Colon Cancer Cells Treated with Resveratrol

Cited by 69 publications

References 51 publications

Oxidative Stress Induced by Curcumin Promotes the Death of Cutaneous T-cell Lymphoma (HuT-78) by Disrupting the Function of Several Molecular Targets

Oxidative Stress Induced by Curcumin Promotes the Death of Cutaneous T-cell Lymphoma (HuT-78) by Disrupting the Function of Several Molecular Targets

Role of Bax in quercetin-induced apoptosis in human prostate cancer cells

trans-Resveratrol induces apoptosis in human breast cancer cells MCF-7 by the activation of MAP kinases pathways

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