Cytochrome c: the Achilles’ heel in apoptosis

Куликов, А. В.; Shilov, E. S.; Mufazalov, Ilgiz A.; Gogvadze, Vladimir; Nedospasov, Sergei A.; Zhivotovsky, Boris

doi:10.1007/s00018-011-0895-z

Cited by 82 publications

(67 citation statements)

References 72 publications

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“…Next, we further characterized the pathway of inducing apoptosis by OSW-1. Our study showed that cytochrome c was released from mitochondria to the cytoplasm which appeared to cause caspase-3 activation, which was recognized as the mitochondrial apoptotic pathway (51)(52)(53). Therefore, these results indicated that OSW-1 inhibited LoVo cells through the intrinsic apoptotic pathway, and was involved in the process of OSW-1 suppression of LoVo cells in vivo based on TuNEL staining.…”

Section: Discussionmentioning

confidence: 57%

Effective cytotoxic activity of OSW-1 on colon cancer by inducing apoptosis in vitro and in vivo

et al. 2017

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Abstract. As a natural compound, Ornithogalum caudatumAit is primarily used as an anti-inflammatory and antitumor agent in Chinese folk medicine. In 1992, OSW-1 was isolated from this compound, which is a new member of cholestane saponin family. In numerous recent studies, OSW-1 has been shown to have powerful cytotoxic anticancer effects against various malignant cells. However, the therapeutic efficacy of OSW-1 on colon cancer and the underlying mechanism are not understood. To explore the mechanism underlying OSW-1 in antitumor therapy, a therapeutic function analysis of OSW-1 on colon cancer was performed in vitro and in vivo. It was shown that with low toxicity on normal colonic cells, OSW-1 suppresses colon cancer cells in vitro and this inhibition was via the intrinsic apoptotic pathway, which increased cellular calcium, changed mitochondrial membrane potential, disrupted mitochondrial morphology, and led to the release of cytochrome c and the activation of caspase-3. Furthermore, in a nude mouse model, OSW-1 had a powerful effect on suppressing colon tumor proliferation without significant side effects through the apoptosis pathway. Taken together, these results demonstrate that OSW-1 is a potential drug for colon cancer treatment.

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Section: Discussionmentioning

confidence: 57%

Effective cytotoxic activity of OSW-1 on colon cancer by inducing apoptosis in vitro and in vivo

et al. 2017

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“…It is well known that Cyt C triggers the activation of caspase cascade in the intrinsic apoptotic pathway if released from mitochondrial membrane gap into cytoplasm (Garrido et al, 2006;Xue et al, 2014). Cyt C is so called the Achilles' heel in apoptosis, for its promotion in the process of apoptosis irreversibly (Kulikov et al, 2012). Dysfunctional mitochondria releases Cyt C, which in turn activates procaspase-9 and forms a complex with the help of the adapter protein Apaf-1.…”

Section: Discussionmentioning

confidence: 99%

Bufalin Induces Mitochondrial Pathway-Mediated Apoptosis in Lung Adenocarcinoma Cells

Ding

Zhang²,

Huang³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: To evaluate the effects of bufalin in A549 human lung adenocarcinoma epithelial cells in vitro and assess the underlying mechanisms. Materials and Methods: Human A549 non-small cell lung cancer (NSCLC) cells were treated with various concentrations of bufalin. Cell proliferation was measured by CCK-8 assay, apoptotic cell percentage was calculated by flow cytometry and morphological change was observed by inverted phase contrast microscopy/transmission electron microscopy. In addition, the membrane potential of mitochondria was detected by JC-1 fluorescence microscopy assay, and the related protein expression of cytochrome C and caspase-3 was analyzed by Western blotting. Results: Bufalin could inhibit the proliferation of A549 cells via induction of apoptosis, with the evidence of characteristic morphological changes in the nucleus and mitochondria. Furthermore, bufalin decreased the mitochondrial membrane potential with up-regulation of cytochrome C in the cytosol, and activation of caspase-3. Conclusions: Bufalin inhibits the proliferation of A549 cells and triggers mitochondria-dependent apoptosis, pointing to therapeutic application for NSCLC.

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“…Apoptosis occurs if the cellular damage incurred during stress exceeds the capacity of the repair mechanisms. In the intrinsic mechanism of apoptosis, mitochondria undergo biochemical and structural changes, leading to the release of various proteins from the intermembrane space, including cytochrome c (cyt c) (25,26). Our recent study showed that during hyperosmotic stress, ANG-induced tiRNAs bind cyt c and competitively inhibit the binding of cyt c to the apoptotic protease-activating factor 1 (APAF1) protein (27).…”

Section: Role Of Tirnas In the Cellular Stress Response And Other Patmentioning

confidence: 99%

The Many Virtues of tRNA-derived Stress-induced RNAs (tiRNAs): Discovering Novel Mechanisms of Stress Response and Effect on Human Health

Saikia

Hatzoglou

2015

Journal of Biological Chemistry

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In mammalian cells, mature tRNAs are cleaved by stress-activated ribonuclease angiogenin to generate 5-and 3-tRNA halves: a novel class of small non-coding RNAs of 30 -40 nucleotides in length. The biogenesis and biological functions of tRNA halves are emerging areas of research. This review will discuss the most recent findings on: (i) the mechanism and regulation of their biogenesis, (ii) their mechanism of action (we will specifically discuss their role in the protein synthesis inhibition and the intrinsic pathway of apoptosis), and (iii) their effects on the human physiology and disease conditions. Recent breakthroughs in high-throughput sequencing have led to a more comprehensive view of the cellular transcriptome. We are now aware of numerous additional non-protein-coding RNA (ncRNA) 3 candidates in all three domains of life, thus indicating a hidden layer of transcriptome complexity (1, 2). A more recent development in our understanding of the complexity of cellular RNomes arose with the exciting discovery that ncRNA transcripts with well described functions, such as the tRNAs, can serve as precursors for downstream cleavage events, generating yet another class of functional RNA fragments. Two major classes of tRNA fragments have been identified in human cells. The 17-26-nucleotide long tRNA-derived RNA fragments (tRFs) are products of precise processing at the 5Ј-or 3Ј-end of mature or precursor tRNAs. The tRF-5 and tRF-3 are derived from terminal ends of mature tRNAs, whereas tRF-1 are 3Ј-trailer sequences of pre-tRNAs (3). The other important class of tRNA fragments found in mammalian cells and tissues is the tRNA-derived stress-induced RNAs (tiRNAs). tiRNAs were first reported in human fetus hepatic tissue (4) and human osteosarcoma cells (U2OS), respectively (5). tRFs and tiRNAs are the newest members of the cellular ncRNA repertoire that are found in several organisms and play prominent roles in various cellular functions (6). These tRNA fragments can be generated in cells under physiological conditions and also produced as part of the cellular stress response (4 -9). In mammalian cells, tiRNAs are produced by the cleavage of mature tRNAs at positions close to the anticodon, giving rise to the 30 -40-nucleotide-long 5Ј-and 3Ј-tRNA halves, a term used interchangeably with 5Ј-and 3Ј-tiRNAs throughout this review. The enzyme responsible for this endonucleolytic cleavage is angiogenin (ANG) (4,5). ANG is a member of the pancreatic RNase superfamily distinguished by its potent in vivo angiogenic activity as well as its prominent role in cancer development and neurodegeneration (10, 11). Here we will review the ANG-induced tRNA halves (tiRNAs), their role in mammalian stress response mechanisms, and other cellular functions. Additionally, we will discuss their potential implications in the pathobiology of human diseases with a special focus on neurodegenerative disorders. ANG-induced tRNA Cleavage in Mammalian CellsEndonucleolytic cleavage of mammalian tRNAs by ANG was reported by two research groups in...

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Cytochrome c: the Achilles’ heel in apoptosis

Cited by 82 publications

References 72 publications

Effective cytotoxic activity of OSW-1 on colon cancer by inducing apoptosis in vitro and in vivo

Effective cytotoxic activity of OSW-1 on colon cancer by inducing apoptosis in vitro and in vivo

Bufalin Induces Mitochondrial Pathway-Mediated Apoptosis in Lung Adenocarcinoma Cells

The Many Virtues of tRNA-derived Stress-induced RNAs (tiRNAs): Discovering Novel Mechanisms of Stress Response and Effect on Human Health

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