Bufalin inhibits human breast cancer tumorigenesis by inducing cell death through the ROS-mediated RIP1/RIP3/PARP-1 pathways

Li, Yanlan; Tian, Xin; Liu, Xiaodan; Gong, Peng

doi:10.1093/carcin/bgy039

Cited by 65 publications

(53 citation statements)

References 32 publications

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“…In addition, bufalin induces death in human cancer cells through the generation of reactive oxygen species, and induces necroptosis through the RIP1/RIP3/PARP-1 pathways. 11 From these findings, we believe that the microbubbles created by HIFU treatment may increase cell damage, especially to the mitochondria, resulting in the generation of reactive oxygen species. The increased reactive oxygen species induce apoptosis in the cancer cells through different pathways.…”

Section: Discussionmentioning

confidence: 89%

“…Many studies have focused on the anticancer activities of bufalin, which have been proven to inhibit cell proliferation and angiogenesis, induce differentiation and apoptosis, reverse drug resistance, alter gene expression in tumor cells, and regulate the body's immune system. [11][12][13][14][15][16] In our previous studies, it was indicated that bufalin significantly inhibited the proliferation, invasion, and metastasis of hepatocellular carcinoma cells through the PI3K/AKT/mTOR/HIF-1α pathway. 17 However, there is no evidence to show whether bufalin could enhance the sensitivity of HIFU.…”

Section: Introductionmentioning

confidence: 98%

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<p>High-intensity focused ultrasound enhances the effect of bufalin by inducing apoptosis in pancreatic cancer cells</p>

Ning

Zhu

Zhang

et al. 2019

OTT

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High-intensity focused ultrasound (HIFU) has the potential to be an effective therapeutic strategy for pancreatic cancer (PC). However, owing to the high malignancy and poor prognosis of PC, the use of HIFU therapy alone is not sufficient to impair the progression of PC. Bufalin, a compound extracted from traditional medicine, is known to inhibit the growth and progression of PC cells. However, the effect of the combination therapy of HIFU plus bufalin (HIFU+bufalin) is still uncertain. Materials and methods: A colony formation assay and flow cytometry were performed to measure the growth and induction of apoptosis in PC cells. Western blotting was used to explore the potential mechanism of HIFU and bufalin therapy. The in vivo efficacy of HIFU+bufalin was tested in a MiaPaCa 2 xenograft model. Results: Bufalin inhibited the growth of PC cells more obviously compared to HIFU. Combining bufalin with HIFU further decreased the growth of MiaPaCa 2 cells compared with single therapy in vitro. Flow cytometry results showed that the percentage of surviving MiaPaCa 2 cells in the bufalin-treated group and the HIFU-treated group was approximately threefold and twofold higher than in the HIFU+bufalin-treated group. Contrasting results were found in Panc-1 cells. Biochemical analysis revealed that HIFU+bufalin treatment elevated PARP expression and increased caspase-8 activation in MiaPaCa 2 and Panc-1 cells. HIFU+bufalin significantly reduced the growth of MiaPaCa 2 tumors compared with HIFU or bufalin treatment alone. HIFU+bufalin treatment decreased Ki67 staining and increased activated caspase-3 and caspase 8 staining, when compared with HIFU or bufalin treatment alone in mouse tumors. Conclusion: HIFU enhanced the effect of bufailn by inducing apoptosis in PC cells. A combination of HIFU and bufalin may be employed as an alternative therapeutic strategy for PC.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 98%

<p>High-intensity focused ultrasound enhances the effect of bufalin by inducing apoptosis in pancreatic cancer cells</p>

Ning

Zhu

Zhang

et al. 2019

OTT

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“…Although ROS-mediated necroptosis is harmful for the recovery of certain diseases, some researches also reported that it has the advantage on repressing the growth of tumor cells. Recently, Li et al revealed that ROS-mediated necroptosis repressed human breast cancer growth possibly due to impaired angiogenesis [56] . Ma et al reported mitochondrial ROS production induced by C/EBP homologous protein (CHOP) promoted A549 human lung cancer cell necroptosis and inhibited lung cancer progression [57] .…”

Section: Discussionmentioning

confidence: 99%

Curcumol induces RIPK1/RIPK3 complex-dependent necroptosis via JNK1/2-ROS signaling in hepatic stellate cells

et al. 2018

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It is generally recognized that hepatic fibrogenesis is an end result of increased extracellular matrix (ECM) production from the activation and proliferation of hepatic stellate cells (HSCs). An in-depth understanding of the mechanisms of HSC necroptosis might provide a new therapeutic strategy for prevention and treatment of hepatic fibrosis. In this study, we attempted to investigate the effect of curcumol on necroptosis in HSCs, and further to explore the molecular mechanisms. We found that curcumol ameliorated the carbon tetrachloride (CCl4)-induced mice liver fibrosis and suppressed HSC proliferation and activation, which was associated with regulating HSC necroptosis through increasing the phosphorylation of receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3). Moreover, curcumol promoted the migration of RIPK1 and RIPK3 into necrosome in HSCs. RIPK3 depletion impaired the anti-fibrotic effect of curcumol. Importantly, we showed that curcumol-induced RIPK3 up-regulation significantly increased mitochondrial reactive oxygen species (ROS) production and mitochondrial depolarization. ROS scavenger, N-acetyl-L-cysteine (NAC) impaired RIPK3-mediated necroptosis. In addition, our study also identified that the activation of c-Jun N-terminal kinase1/2 (JNK1/2) was regulated by RIPK3, which mediated curcumol-induced ROS production. Down-regulation of RIPK3 expression, using siRIPK3, markedly abrogated JNK1/2 expression. The use of specific JNK1/2 inhibitor (SP600125) resulted in the suppression of curcumol-induced ROS production and mitochondrial depolarization, which in turn, contributed to the inhibition of curcumol-triggered necroptosis. In summary, our study results reveal the molecular mechanism of curcumol-induced HSC necroptosis, and suggest a potential clinical use of curcumol-targeted RIPK1/RIPK3 complex-dependent necroptosis via JNK1/2-ROS signaling for the treatment of hepatic fibrosis.

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“…This suggests that inducing necroptosis could be used as a second-line treatment in cancer patients after the development of resistance to apoptosis [116][117][118]. Natural compounds such as shikonin (a component of a Chinese herbal medicine), staurosporine (an alkaloid extracted from the bacterium Streptomyces staurosporeus), neoalbaconol (a compound of a fungus), and bufalin (an ingredient of a Chinese medicine isolated from the skin and glands of toads) were also able to trigger necroptosis, with anti-tumoral outcomes [6,[119][120][121]. Recent results of some clinical studies confirmed that necroptosis promotes natural or therapy-driven anti-cancer immunosurveillance in different neoplasms, including breast and ovarian carcinoma [3].…”

Section: Necroptosis-based Therapies For Cholangiocarcinomamentioning

confidence: 99%

Necroptosis in Cholangiocarcinoma

Sarcognato

Jong

Fabris

et al. 2020

Cells

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Necroptosis is a type of regulated cell death that is increasingly being recognized as a relevant pathway in different pathological conditions. Necroptosis can occur in response to multiple stimuli, is triggered by the activation of death receptors, and is regulated by receptor-interacting protein kinases 1 and 3 and mixed-lineage kinase domain-like, which form a regulatory complex called the necrosome. Accumulating evidence suggests that necroptosis plays a complex role in cancer, which is likely context-dependent and can vary among different types of neoplasms. Necroptosis serves as an alternative mode of programmed cell death overcoming apoptosis and, as a pro-inflammatory death type, it may inhibit tumor progression by releasing damage-associated molecular patterns to elicit robust cross-priming of anti-tumor CD8+ T cells. The development of therapeutic strategies triggering necroptosis shows great potential for anti-cancer therapy. In this review, we summarize the current knowledge on necroptosis and its role in liver biliary neoplasms, underlying the potential of targeting necroptosis components for cancer treatment.Cells 2020, 9, 982 2 of 18 (RIPK3) and mixed lineage kinase domain-like (MLKL) [4]. Therefore, necroptosis is an alternative mode of CD when the caspase-8-dependent apoptotic pathway is blocked. It is now well-established that various stimuli can initiate necroptosis, including intra-and extracellular factors, such as tumor necrosis factor α (TNFα) and reactive oxygen species (ROS) [5].A hallmark of cancer is the ability of malignant cells to evade apoptosis. Therefore, the induction of necroptosis could be an alternative strategy for killing cancer cells. Several therapeutics able to affect the necroptotic cascade have recently been developed, and a few of them are already in phase 1 trials for the treatment of inflammatory diseases. Moreover, necroptosis modulation is becoming the target of several new anti-cancer strategies. In fact, it has been demonstrated that apoptosis-resistant tumors respond to necroptosis, and that necroptosis can create an immunogenic microenvironment that enhances tumor clearance [6]. These aspects will be further discussed in the following chapters.Herein, we will discuss the general aspects of necroptosis and what is currently known on its involvement in cholangiocarcinoma (CCA), in order to provide perspectives for future studies in this relatively new field. Overview on Types of Cell DeathIn 2005, the Nomenclature Committee on Cell Death (NCCD) defined the first CD classification purely based on morphological criteria. This classification included three major forms of CD: types I, II, and III [7]. Type I CD, termed apoptosis, exhibits cell shrinkage, membrane blebbing, DNA fragmentation, chromatin condensation, and the formation of apoptotic bodies. Apoptosis is a form of RCD and responds to two different death signals: damage from inside the cell, such as DNA damage, which elicits an intrinsic pathway, and extracellular stimuli, such as TNFα and the Fas ligand, ...

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Bufalin inhibits human breast cancer tumorigenesis by inducing cell death through the ROS-mediated RIP1/RIP3/PARP-1 pathways

Cited by 65 publications

References 32 publications

<p>High-intensity focused ultrasound enhances the effect of bufalin by inducing apoptosis in pancreatic cancer cells</p>

<p>High-intensity focused ultrasound enhances the effect of bufalin by inducing apoptosis in pancreatic cancer cells</p>

Curcumol induces RIPK1/RIPK3 complex-dependent necroptosis via JNK1/2-ROS signaling in hepatic stellate cells

Necroptosis in Cholangiocarcinoma

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