Up-regulation of death receptor 4 and 5 by celastrol enhances the anti-cancer activity of TRAIL/Apo-2L

Zhu, Hong; Liu, Xiao Wen; Ding, Wan Jing; Xu, Danfeng; Zhao, Yu; Lü, Wei; He, Qiao; Yang, Bo

doi:10.1016/j.canlet.2010.04.030

Cited by 52 publications

(40 citation statements)

References 35 publications

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“…A previous study has identified that celastrol treatment resulted in a significant activation of p38 and ERK and a marginal activation of stress-activated protein kinases/JNK in a dose-and time-dependent manner (17). Zhu et al (20) hypothesized that DR4 and DR5 are involved in the sensitization of celastrol-treated cells to TRAIL/Apo-2L-induced apoptosis, in a p38-independent manner. In addition, Choi et al (21) observed that celastrol reduced the extent of rotenone-induced generation of reactive oxygen species and mitochondrial membrane potential loss by inhibiting p38 activation in the SH-SY5Y human neuroblastoma cell line.…”

Section: Discussionmentioning

confidence: 98%

Celastrol-induced apoptosis in human nasopharyngeal carcinoma is associated with the activation of the death receptor and the mitochondrial pathway

et al. 2017

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Abstract. Nasopharyngeal carcinoma (NPC) is a cancer that arises from the epithelium of the nasopharynx. Celastrol is a triterpene from traditional Chinese medicine, which demonstrates anti-proliferative activity in several cancer cell lines. However, the effect of celastrol on human NPC and the underlying mechanisms are not yet elucidated. The present study investigated whether celastrol induced apoptosis in human NPC cells, and the underlying molecular mechanisms were explored. Celastrol decreased the viability of HONE-1 and NPC-039 cells in a dose-dependent manner, and induced G1 and G2/M phase cell cycle arrest. The level of cleaved caspases-3, -8, and -9 and poly (ADP-ribose) polymerase 1 increased in cells treated with celastrol. There was an increase in active Bcl-2-like 11 isoform S, Bcl-2-associated X, Bcl-2 antagonist/killer and truncated BH3-interacting death antagonist, and the levels of the anti-apoptotic Bcl-2 and Bcl-2-like 1 decreased. Celastrol induced an increase in Fas, Fas-associated via death domain, TNF receptor superfamily members (TNRSF) 1A and 10B, and TNFRSF1A associated via death domain, and induced a dose-dependent reduction in mitochondrial membrane potential. Celastrol inhibited activation of mitogen-activated protein kinase (MAPK) 1/3 and 14, and induced MAPK 8/9 activation. The results indicated that celastrol induced apoptosis through the death receptor and the mitochondrial pathway in human NPC cells, and is a promising candidate in the development of drugs against NPC. IntroductionNasopharyngeal carcinoma (NPC) is a cancer that arises from the epithelium of nasopharynx. This cancer is uncommon in Europe and America, and its incidence is higher in Africa and Southeast Asia (1). Its unique epidemiology, pathogenesis and association with the Epstein-Barr virus make it distinct from other types of head and neck cancer. Although NPC is reported to respond well to radiation therapy, chemotherapy also has a function in the current treatment protocol (2). For cases that have spread beyond the nasopharynx (i.e., cancer stages II, III, IVA and IVB), the addition of chemotherapy is common. Typically, platinum based agents, including cisplatin or carboplatin are used to treat NPC alongside fluorouracil (3). However, these medications also harm normal cells, causing side effects that include a decrease in white blood cells, anemia, kidney toxicity and nausea.Apoptosis, the process of programmed cell death, is a crucial self-defense mechanism for the human body to counteract cancerous cells. A number of existing chemotherapeutic agents aim to initiate the apoptosis cascade for an anti-tumor effect (4,5). However, as the disease progresses, certain cancer cell populations become resistant to chemotherapeutic agents and the efficacy of chemotherapy gradually deteriorates. Therefore, developing novel chemotherapeutic agents against NPC is crucial.Tripterygium wilfordii, also known as thunder god vine, is an herb traditionally used in Asia to treat various diseases, including tissue inflammation...

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Section: Discussionmentioning

confidence: 98%

Celastrol-induced apoptosis in human nasopharyngeal carcinoma is associated with the activation of the death receptor and the mitochondrial pathway

et al. 2017

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“…Flavokawain B induced apoptosis via enhancing DR 5 expression in prostate cancer cell line 22) . Celastrol also enhanced anti-cancer effect of TNF-related apoptosis-inducing ligand(TRAIL)/Apo-2L via upregulation of DR 4 and DR 5 expression in human ovarian and colon cancer cells 23) . In addition, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate exerted anticancer activity via inducing DR-mediated apoptosis in the lung cancer 32) .…”

Section: ⅳ Discussionmentioning

confidence: 99%

“…In the extrinsic pathway, apoptosis is generally activated by death receptor(DR)s of tumor necrosis factor(TNF) family such as Fas, tumor necrosis factor receptor(TNFR)-1, TNFR-2, DR 3, DR 4, DR 5 and DR 6, which are implicated in various kinds of cancers [12][13][14][15][16][17][18][19] . According to the several previous reports [20][21][22][23] , it is true that DR mediated apoptosis has emerged as an effective strategy for cancer therapy. However, certain types of cancer cells are intrinsically resistant to DR-mediated apoptosis.…”

Section: ⅰ Introductionmentioning

confidence: 99%

Inhibitory Effect of Bee Venom Toxin on Lung Cancer NCI H460 Cells Growth Through Induction of Apoptosis via Death Receptor Expressions

Hur

Song

2014

The Acupuncture

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[Abstract]Objectives : I investigated whether bee venom inhibit cell growth through enhancement of death receptor expressions in the human lung cancer cells, NCI-H460. Methods : Bee venom(1-5 μg/ml) inhibited the growth of NCI-H460 lung cancer cells by the induction of apoptotic cell death in a dose dependent manner. Results : Consistent with apoptotic cell death, expression of TNF-R1, TNF-R2, FAS, death receptors(DR) 3, 4, 5 and 6 was increased in the cells. Expression of DR downstream pro-apoptotic proteins including Caspase-8, -3, -9 was upregulated and Bax was concomitantly overwhelmed the expression of Bcl-2. NF-kB were inhibited by treatment with bee venom in NCI-H460 cells through TNF response change led by TNF-R1 and TNF-R2. Conclusions : These results suggest that bee venom should exert anti-tumor effect through induction of apoptotic cell death in NCI-H460 human lung cancer cells via enhancement of death receptor expression, and that bee venom could be a promising agent for preventing and treating lung cancer.

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“…We have also recently demonstrated that celastrol can indeed potentiate the apoptotic effects of botezomib and thalidomide by suppression of both NF-jB and STAT3 activation in multiple myeloma cells [92]. Celastrol up-regulates death receptor 4 (DR4) and 5 (DR5) expression at mRNA, and cell surface receptor levels, and knockdown of DR4 or DR5 attenuates the PARP cleavage caused by the combination of celastrol and TRAIL/Apo-2L, denoting the critical roles of DR induction in this sensitization of cells to apoptosis [91]. Celastrol analogs, pristimerin and dihydrocelastrol, have been shown to induce heat shock response and protect against lethal stress in HeLa cells and SH-SY5Y neuronal cells [98].…”

Section: Celastrolmentioning

confidence: 96%

“…The in vivo anti-inflammatory effects of this triterpene have been demonstrated in animal models of collagen-induced arthritis, rheumatoid arthritis, Alzheimer's disease, asthma, and systemic lupus erythematosus [83][84][85]. This triterpene has also been found to suppress tumor initiation, promotion and metastasis in various cancer models through modulation of multiple pro-inflammatory cytokines, chemokines, enzymes and transcription factors [4,[86][87][88][89][90][91]. For example, celastrol has been shown to inhibit the proliferation of a wide variety of tumor cells [6,83,[92][93][94].…”

Section: Celastrolmentioning

confidence: 98%

Targeted inhibition of tumor proliferation, survival, and metastasis by pentacyclic triterpenoids: Potential role in prevention and therapy of cancer

et al. 2012

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a b s t r a c tOver the last two decades, extensive research on plant-based medicinal compounds has revealed exciting and important pharmacological properties and activities of triterpenoids. Fruits, vegetables, cereals, pulses, herbs and medicinal plants are all considered to be biological sources of these triterpenoids, which have attracted great attention especially for their potent anti-inflammatory and anti-cancer activities. Published reports in the past have described the molecular mechanism(s) underlying the various biological activities of triterpenoids which range from inhibition of acute and chronic inflammation, inhibition of tumor cell proliferation, induction of apoptosis, suppression of angiogenesis and metastasis. However systematic analysis of various pharmacological properties of these important classes of compounds has not been done. In this review, we describe in detail the pre-clinical chemopreventive and therapeutic properties of selected triterpenoids that inhibit multiple intracellular signaling molecules and transcription factors involved in the initiation, progression and promotion of various cancers. Molecular targets modulated by these triterpenoids comprise, cytokines, chemokines, reactive oxygen intermediates, oncogenes, inflammatory enzymes such as COX-2, 5-LOX and MMPs, anti-apoptotic proteins, transcription factors such as NF-jB, STAT3, AP-1, CREB, and Nrf2 (nuclear factor erythroid 2-related factor) that regulate tumor cell proliferation, transformation, survival, invasion, angiogenesis, metastasis, chemoresistance and radioresistance. Finally, this review also analyzes the potential role of novel synthetic triterpenoids identified recently which mimic natural triterpenoids in physical and chemical properties and are moving rapidly from bench to bedside research.

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Up-regulation of death receptor 4 and 5 by celastrol enhances the anti-cancer activity of TRAIL/Apo-2L

Cited by 52 publications

References 35 publications

Celastrol-induced apoptosis in human nasopharyngeal carcinoma is associated with the activation of the death receptor and the mitochondrial pathway

Celastrol-induced apoptosis in human nasopharyngeal carcinoma is associated with the activation of the death receptor and the mitochondrial pathway

Inhibitory Effect of Bee Venom Toxin on Lung Cancer NCI H460 Cells Growth Through Induction of Apoptosis via Death Receptor Expressions

Targeted inhibition of tumor proliferation, survival, and metastasis by pentacyclic triterpenoids: Potential role in prevention and therapy of cancer

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