Mitochondria-mediated apoptosis in mammals

Xiong, Shunbin; Mu, Tianyang; Wang, Guowen; Jiang, Xuejun

doi:10.1007/s13238-014-0089-1

Cited by 347 publications

(279 citation statements)

References 165 publications

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“…The extrinsic pathway is triggered by death receptors (Fas, TNFR, and DR5) in response to ligand binding, leading to caspase-8 activation (25). The key event of the intrinsic pathway is the permeabilization of the mitochondrial outer membrane, which occurs in response to various stimuli, and is regulated by many cytoplasmic proteins including family members of Bcl-2 (26). Bcl-2 is a thiol-containing protein that prevents apoptosis through the negative regulation of Bax and Bak mitochondrial translocation (27).…”

Section: Discussionmentioning

confidence: 99%

Cambogin Induces Caspase-Independent Apoptosis through the ROS/JNK Pathway and Epigenetic Regulation in Breast Cancer Cells

Shen

Xie

Wang

et al. 2015

Molecular Cancer Therapeutics

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Cambogin is a polycyclic polyprenylated acylphoroglucinol (PPAP) from the Garcinia genus, which has been used traditionally for cancer treatment across Southeastern Asia. In this study, we found that cambogin inhibited breast cancer cell proliferation and induced cell apoptosis in vitro. Cambogin induced the activation of the caspase-independent mitochondrial apoptotic pathway, as indicated by an increase in the ratio of Bax/Bcl-2 and the nuclear translocation of apoptosis inducing factor (AIF). Two-dimensional gel electrophoresis and mass spectrometry revealed that the expression of proteins involving in the radical oxygen species (ROS) pathway was among the most affected upon cambogin treatment. Cambogin enhanced cellular ROS production, and induced the activation of the ASK1-MKK4/MKK7-JNK/SAPK signaling pathway. Pretreatment with ROS scavenger N-acetylcysteine (NAC), an antioxidant, or the JNK inhibitor SP600125 was able to restore cell viability in the presence of cambogin. Importantly, cambogin treatment led to the activation of activating transcription factor-2 (ATF-2) and the trimethylation of histone H3K9 in the activator protein 1 (AP-1) binding region of the Bcl-2 gene promoter. Finally, cambogin exhibited a potential antitumor effect in MCF-7 breast cancer xenografts without apparent toxicity. Taken in conjunction, the present study indicates that cambogin can induce breast adenocarcinoma cell apoptosis and therefore represents therapeutic potential for cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Cambogin Induces Caspase-Independent Apoptosis through the ROS/JNK Pathway and Epigenetic Regulation in Breast Cancer Cells

Shen

Xie

Wang

et al. 2015

Molecular Cancer Therapeutics

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“…Mitochondria play a critical role in antiviral responses because they mediate the induction of apoptosis as well as expression of type I IFNs. Apoptosis is controlled by members of the B-cell leukemia/ lymphoma 2 (BCL2) family, which mainly localize on mitochondrial surfaces (5). Proapoptotic BCL2 family members such as BCL2-associated X protein (BAX) and BCL2 antagonist/killer 1 (BAK1) induce mitochondrial outer membrane permeabilization to activate caspase-9, leading to the induction of cell death, whereas the anti-apoptotic BCL2 family members inhibit BAX-and BAK1-dependent induction of mitochondrial outer membrane permeabilization.…”

mentioning

confidence: 99%

Mitochondrial damage elicits a TCDD-inducible poly(ADP-ribose) polymerase-mediated antiviral response

Kozaki

Komano

Kanbayashi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The innate immune system senses RNA viruses by pattern recognition receptors (PRRs) and protects the host from virus infection. PRRs mediate the production of immune modulatory factors and direct the elimination of RNA viruses. Here, we show a unique PRR that mediates antiviral response. Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP ribose) polymerase (TIPARP), a Cysteine3 Histidine (CCCH)-type zinc finger-containing protein, binds to Sindbis virus (SINV) RNA via its zinc finger domain and recruits an exosome to induce viral RNA degradation. TIPARP typically localizes in the nucleus, but it accumulates in the cytoplasm after SINV infection, allowing targeting of cytoplasmic SINV RNA. Redistribution of TIPARP is induced by reactive oxygen species (ROS)-dependent oxidization of the nuclear pore that affects cytoplasmic-nuclear transport. BCL2-associated X protein (BAX) and BCL2 antagonist/killer 1 (BAK1), B-cell leukemia/lymphoma 2 (BCL2) family members, mediate mitochondrial damage to generate ROS after SINV infection. Thus, TIPARP is a viral RNA-sensing PRR that mediates antiviral responses triggered by BAX-and BAK1-dependent mitochondrial damage.innate immunity | antiviral response | mitochondrial damage | RNA degradation | reactive oxygen species

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“…The interaction between members of the Bcl-2 family regulates mitochondrial outer membrane permeabilization and thus induces cell apoptosis 11,21…”

Section: Discussionmentioning

confidence: 99%

Knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha increased apoptosis of human endometrial cancer HEC-1A cells

Yang¹,

Yang²,

Líu³

et al. 2016

OTT

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BackgroundPeroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) coactivates multiple transcription factors and regulates several metabolic processes. In this study, we focused on the roles of PGC-1α in the apoptosis of endometrial cancer HEC-1A cells.Materials and methodsPGC-1a expression in the HEC-1A cells was detected with real-time polymerase chain reaction and Western blot. Small interfering RNA directed against PGC-1α was designed and synthesized, and RNA interference technology was used to knock down PGC-1α mRNA and protein expression. Cell apoptosis, cell cycle, and mitochondrial membrane potential were then analyzed using flow cytometry. The expression of apoptotic proteins, Bcl-2 and Bax, was detected with Western blot.ResultsThe specific downregulation of PGC-1α expression in the HEC-1A cells increased their apoptosis through the mitochondrial apoptotic pathway by reducing the expression of Bcl-2 and increasing the expression of Bax.ConclusionThese results suggest that PGC-1α influences the apoptosis of HEC-1A cells and also provides a molecular basis for further investigation of the apoptotic mechanism in human endometrial cancer.

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Mitochondria-mediated apoptosis in mammals

Cited by 347 publications

References 165 publications

Cambogin Induces Caspase-Independent Apoptosis through the ROS/JNK Pathway and Epigenetic Regulation in Breast Cancer Cells

Cambogin Induces Caspase-Independent Apoptosis through the ROS/JNK Pathway and Epigenetic Regulation in Breast Cancer Cells

Mitochondrial damage elicits a TCDD-inducible poly(ADP-ribose) polymerase-mediated antiviral response

Knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha increased apoptosis of human endometrial cancer HEC-1A cells

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