Snake venom toxin from Vipera lebetina turanica sensitizes cancer cells to TRAIL through ROS- and JNK-mediated upregulation of death receptors and downregulation of survival proteins

Park, Mi Hee; Jo, Miran; Won, Dohee; Song, Ho Sueb; Song, Min Jong; Hong, Jin Tae

doi:10.1007/s10495-012-0759-5

Cited by 20 publications

(16 citation statements)

References 44 publications

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“…Curcumin sensitizes TRAIL-resistant prostate cancer cells in xenograft model through DR4 and DR5 expression and inhibition of p-p65 (Shankar et al 2008). Previously, we found that the combination of SVT and TRAIL increases DR4 and DR5 expression in TRAIL-resistant colon cancer cells (Park et al 2012b). Therefore, it is possible that SVT can overcome resistance to TRAIL through an inactivation of NF-κB and expression of DR3 and DR5 (Park et al 2012b).…”

Section: Discussionmentioning

confidence: 91%

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Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression

et al. 2014

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We previously found that snake venom toxin inhibits nuclear factor kappa B (NF-κB) activity in several cancer cells. NF-κB is implicated in cancer cell growth and chemoresistance. In our present study, we investigated whether snake venom toxin (SVT) inhibits NF-κB, thereby preventing human cervical cancer cell growth (Ca Ski and C33A). SVT (0-12 μg/ml) inhibited the growth of cervical cancer cells by the induction of apoptotic cell death. These inhibitory effects were associated with the inhibition of NF-κB activity. However, SVT dose dependently increased the expression of death receptors (DRs): DR3, DR5 and DR downstream pro-apoptotic proteins. Exploration of NF-κB inhibitor (Phenylarsine oxide, 0.1 μM) synergistically further increased SVT-induced DR3 and DR5 expressions accompanied with further inhibition of cancer cells growth. Moreover, deletion of DR3 and DR5 by small interfering RNA significantly abolished SVT-induced cell growth inhibitory effects, as well as NF-κB inactivation. Using TNF-related apoptosis-inducing ligand resistance cancer cells (A549 and MCF-7), we also found that SVT enhanced the susceptibility of chemoresistance of these cancer cells through down-regulation of NF-κB, but up-regulation of DR3 and DR5. In vivo study also showed that SVT (0.5 and 1 mg/kg) inhibited tumor growth accompanied with inactivation of NF-κB. Thus, our present study indicates that SVT could be applicable as an anticancer agent for cervical cancer, or as an adjuvant agent for chemoresistant cancer cells.

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Section: Discussionmentioning

confidence: 91%

“…Previously, we found that the combination of SVT and TRAIL increases DR4 and DR5 expression in TRAIL-resistant colon cancer cells (Park et al 2012b). Therefore, it is possible that SVT can overcome resistance to TRAIL through an inactivation of NF-κB and expression of DR3 and DR5 (Park et al 2012b).…”

Section: Discussionmentioning

confidence: 94%

Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression

et al. 2014

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“…125 However, other natural compounds such as SVT (snake venom toxin from vipera lebetina turanica), ursolic acid (a pentacyclin triterpene), capsazepine (the active ingredient of chilli pepper), and tricetin (a flavonoid derivative found in Myrtaceae pollen and Eucalyptus Honey) induce DRs mediated by JNK1/2 activation through production of ROS. [126][127][128][129] DRs can also be upregulated by diverse natural compounds through the activation of p38 signaling cascade. Another natural agent, lupulone, a b-acid largely present in hops (Humulus lupulus l), can significantly enhance the expression of p38, which plays a major role in the activation of p53 and the TRAIL-DR apoptotic pathway in SW620 human colon cancer-derived metastatic cells.…”

Section: Natural Compounds That Can Sensitize Tumor Cells To Trailmentioning

confidence: 99%

Targeting TNF-related apoptosis-inducing ligand (TRAIL) receptor by natural products as a potential therapeutic approach for cancer therapy

Dai

Zhang

Arfuso

et al. 2015

Exp Biol Med (Maywood)

165

109

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to selectively induce apoptotic cell death in various tumor cells by engaging its death-inducing receptors (TRAIL-R1 and TRAIL-R2). This property has led to the development of a number of TRAIL-receptor agonists such as the soluble recombinant TRAIL and agonistic antibodies, which have shown promising anticancer activity in preclinical studies. However, besides activating caspase-dependent apoptosis in several cancer cells, TRAIL may also activate nonapoptotic signal transduction pathways such as nuclear factor-kappa B, mitogen-activated protein kinases, AKT, and signal transducers and activators of transcription 3, which may contribute to TRAIL resistance that is being now frequently encountered in various cancers. TRAIL resistance can be overcome by the application of efficient TRAILsensitizing pharmacological agents. Natural compounds have shown a great potential in sensitizing cells to TRAIL treatment through suppression of distinct survival pathways. In this review, we have summarized both apoptotic and nonapoptotic pathways activated by TRAIL, as well as recent advances in developing TRAIL-receptor agonists for cancer therapy. We also briefly discuss combination therapies that have shown great potential in overcoming TRAIL resistance in various tumors.

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“…This increment of MDA could be produced due the arachidonic acid release after PLA 2 catalysis [11]. Moreover, the newly produced arachidonic acid could be oxidized by H 2 O 2 produced by the LAAO catalysis [25].…”

Section: Resultsmentioning

confidence: 99%

“…SVMPs, major components in most Crotalid venoms, have a relevant role in venom-induced local damage. The lethality of this venom is due to the high activity of PLA 2 that hydrolyzes phospholipids and releases arachidonic acid, which, in turn, generates toxic reactive oxygen species (ROS) [10, 11]. This reaction results in lipid peroxidation and leads to cellular damage [12].…”

Section: Introductionmentioning

confidence: 99%

Rattlesnake Crotalus molossus nigrescens venom induces oxidative stress on human erythrocytes

Meléndez‐Martínez

Muñoz

Barraza-Garza

et al. 2017

J Venom Anim Toxins Incl Trop Dis

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BackgroundGlobally, snake envenomation is a well-known cause of death and morbidity. In many cases of snakebite, myonecrosis, dermonecrosis, hemorrhage and neurotoxicity are present. Some of these symptoms may be provoked by the envenomation itself, but others are secondary effects of the produced oxidative stress that enhances the damage produced by the venom toxins. The only oxidative stress effect known in blood is the change in oxidation number of Fe (from ferrous to ferric) in hemoglobin, generating methemoglobin but not in other macromolecules. Currently, the effects of the overproduction of methemoglobin derived from snake venom are not extensively recorded. Therefore, the present study aims to describe the oxidative stress induced by Crotalus molossus nigrescens venom using erythrocytes.MethodsHuman erythrocytes were washed and incubated with different Crotalus molossus nigrescens venom concentrations (0–640 μg/mL). After 24 h, the hemolytic activity was measured followed by attenuated total reflectance-Fourier transform infrared spectroscopy, non-denaturing PAGE, conjugated diene and thiobarbituric acid reactive substances determination.ResultsLow concentrations of venom (<10 μg/mL) generates oxyhemoglobin release by hemolysis, whereas higher concentrations produced a hemoglobin shift of valence, producing methemoglobin (>40 μg/mL). This substance is not degraded by proteases present in the venom. By infrared spectroscopy, starting in 80 μg/mL, we observed changes in bands that are associated with protein damage (1660 and 1540 cm−1) and lipid peroxidation (2960, 2920 and 1740 cm−1). Lipid peroxidation was confirmed by conjugated diene and thiobarbituric acid reactive substance determination, in which differences were observed between the control and erythrocytes treated with venom.Conclusions Crotalus molossus nigrescens venom provokes hemolysis and oxidative stress, which induces methemoglobin formation, loss of protein structure and lipid peroxidation.

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Snake venom toxin from Vipera lebetina turanica sensitizes cancer cells to TRAIL through ROS- and JNK-mediated upregulation of death receptors and downregulation of survival proteins

Cited by 20 publications

References 44 publications

Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression

Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression

Targeting TNF-related apoptosis-inducing ligand (TRAIL) receptor by natural products as a potential therapeutic approach for cancer therapy

Rattlesnake Crotalus molossus nigrescens venom induces oxidative stress on human erythrocytes

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