Resibufogenin suppresses colorectal cancer growth and metastasis through RIP3-mediated necroptosis

Han, Qiuju; Ma, Ye; Wang, Hao; Dai, Yu; Chen, Chuansheng; Liu, Yawei; Jing, Linyuan; Sun, Xuegang

doi:10.1186/s12967-018-1580-x

Cited by 94 publications

(72 citation statements)

References 33 publications

(42 reference statements)

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“…It has been shown to exhibit anti-proliferative effects in multiple cancer cells [142–144]. Recently, Han et al [110] have reported that resibufogenin was shown to suppress the growth and metastasis of colorectal cancer by inducing RIPK3 necroptosis both in vitro and in vivo through upregulating RIPK3 and MLKL protein at Ser358. The study also demonstrated that resibufogenin may activate three key metabolic enzymes, including glycogen phosphorylase (PYGL), glutamine synthetase (GLUL), and glutamate dehydrogenase (GLUDl) in a RIPK3 dependent manner, and resibufogenin was also found to suppress liver metastasis of colorectal cancer in mouse models [110].…”

Section: Natural Compoundsmentioning

confidence: 99%

The role of necroptosis in cancer biology and therapy

et al. 2019

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Apoptosis resistance is to a large extent a major obstacle leading to chemotherapy failure during cancer treatment. Bypassing the apoptotic pathway to induce cancer cell death is considered to be a promising approach to overcoming this problem. Necroptosis is a regulated necrotic cell death modality in a caspase-independent fashion and is mainly mediated by Receptor-Interacting Protein 1 (RIP1), RIP3, and Mixed Lineage Kinase Domain-Like (MLKL). Necroptosis serves as an alternative mode of programmed cell death overcoming apoptosis resistance and may trigger and amplify antitumor immunity in cancer therapy. The role of necroptosis in cancer is complicated. The expression of key regulators of the necroptotic pathway is generally downregulated in cancer cells, suggesting that cancer cells may also evade necroptosis to survive; however, in certain types of cancer, the expression level of key mediators is elevated. Necroptosis can elicit strong adaptive immune responses that may defend against tumor progression; however, the recruited inflammatory response may also promote tumorigenesis and cancer metastasis, and necroptosis may generate an immunosuppressive tumor microenvironment. Necroptosis also reportedly promotes oncogenesis and cancer metastasis despite evidence demonstrating its antimetastatic role in cancer. In addition, necroptotic microenvironments can direct lineage commitment to determine cancer subtype development in liver cancer. A plethora of compounds and drugs targeting necroptosis exhibit potential antitumor efficacy, but their clinical feasibility must be validated. Better knowledge of the necroptotic pathway mechanism and its physiological and pathological functions is urgently required to solve the remaining mysteries surrounding the role of necroptosis in cancer. In this review, we briefly introduce the molecular mechanism and characteristics of necroptosis, the interplay between necroptosis and other cell death mechanisms, crosstalk of necroptosis and metabolic signaling and detection methods. We also summarize the intricate role of necroptosis in tumor progression, cancer metastasis, prognosis of cancer patients, cancer immunity regulation, cancer subtype determination and cancer therapeutics.

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Section: Natural Compoundsmentioning

confidence: 99%

The role of necroptosis in cancer biology and therapy

et al. 2019

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“…A recent study also showed that resibufogenin suppresses growth and metastasis of CRC through RIPK3-mediated necroptosis. This kind of effect can be reduced by RIPK3 deficiency rather than the use of z-VAD, a pan-caspase general inhibitor, which confirms the role of necroptosis in the treatment of CRC[ 36 ].…”

Section: Necroptosis and Crcmentioning

confidence: 74%

Necroptosis in inflammatory bowel disease and other intestinal diseases

Ning

Lou

et al. 2018

WJCC

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For a long time, it was believed that apoptosis and necrosis were the main pathways for cell death, but a growing body of research has shown that there are other pathways. Among these, necroptosis, a regulatory caspase-independent, programmed cell death pathway, is supposed to be of importance in the pathogenesis of many diseases. The mechanism of regulating, inducing and blocking necroptosis is a complex process that involves expression and regulation of a series of molecules including receptor interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase like protein. By blocking or downregulating expression of key molecules in the necroptotic pathway, intestinal inflammation can be affected to some extent. In this paper, we introduce the concept of necroptosis, its main pathway, and its impact on the pathogenesis of inflammatory bowel disease (IBD) and other intestinal diseases, to explore new drug targets for intestinal diseases, including IBD.

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“…Han et al suggested that it can initiate necroptosis to suppress metastasis in both human CRC HCT116 and SW480 cells and in an in vivo xenograft mouse model through the elevation of RIP3. In addition, it also promotes the expression of PYGL, GLUD1 and GLUL, which are important enzymes, via RIP3 to generate ROS [120].…”

Section: Treatments Targeting Both Ros and Necroptosismentioning

confidence: 99%

The Role of Necroptosis in ROS-Mediated Cancer Therapies and Its Promising Applications

Hsu

Chang

Lin

et al. 2020

Cancers

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Over the past decades, promising therapies targeting different signaling pathways have emerged. Among these pathways, apoptosis has been well investigated and targeted to design diverse chemotherapies. However, some patients are chemoresistant to these therapies due to compromised apoptotic cell death. Hence, exploring alternative treatments aimed at different mechanisms of cell death seems to be a potential strategy for bypassing impaired apoptotic cell death. Emerging evidence has shown that necroptosis, a caspase-independent form of cell death with features between apoptosis and necrosis, can overcome the predicament of drug resistance. Furthermore, previous studies have also indicated that there is a close correlation between necroptosis and reactive oxygen species (ROS); both necroptosis and ROS play significant roles both under human physiological conditions such as the regulation of inflammation and in cancer biology. Several small molecules used in experiments and clinical practice eliminate cancer cells via the modulation of ROS and necroptosis. The molecular mechanisms of these promising therapies are discussed in detail in this review.

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Resibufogenin suppresses colorectal cancer growth and metastasis through RIP3-mediated necroptosis

Cited by 94 publications

References 33 publications

The role of necroptosis in cancer biology and therapy

The role of necroptosis in cancer biology and therapy

Necroptosis in inflammatory bowel disease and other intestinal diseases

The Role of Necroptosis in ROS-Mediated Cancer Therapies and Its Promising Applications

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