Anticancer drug-induced apoptosis in human monocytic leukemic cell line U937 requires activation of endonuclease(s)

Shrivastava, Punya; Sodhi, Ajit; Ranjan, Priya

doi:10.1097/00001813-200001000-00007

Cited by 17 publications

(13 citation statements)

References 32 publications

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“…The role of endonucleases in the apoptosis of cancer cell death was demonstrated in several studies, however the major endonuclease responsible for breast epithelium and breast cancer cell death was not determined [9,10]. In the current study, we presented evidence that EndoG is the major endonuclease in breast epithelium and breast cancer cells.…”

Section: Discussionmentioning

confidence: 47%

“…Anticancer drugs induce apoptosis in cancer cells through endonuclease-mediated DNA fragmentation [9,10], while the inhibition of endonucleases has a protective effect on cancer cell death [10]. Cell death endonucleases include deoxyribonuclease I (DNase I) [11], deoxyribonuclease II (DNase II) [12], endonuclease G (EndoG) [13], caspase-activated DNase (CAD) [14], and DNase gamma [15].…”

Section: Introductionmentioning

confidence: 99%

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Endonuclease G promotes cell death of non-invasive human breast cancer cells

Basnakian

Apostolov

Yin

et al. 2006

Experimental Cell Research

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The invasiveness of breast cancer cells was shown to be associated with the suppressed ability to develop apoptosis. The role of cell death DNases/endonucleases has not been previously examined in relation with the invasiveness of breast cancer cells. We have compared the activity of the endonucleases in seven human breast cancer cell lines different in the level of invasiveness and differentiation. The invasiveness of cell lines was confirmed by an in vitro Matrigel-based assay. The total endonuclease activity in the differentiated non-invasive (WDNI) cell lines was higher than that in the poorly differentiated invasive (PDI) cells. The expression of EndoG strongly correlated with the degree of estrogen receptor expression and showed an inverse correlation with vimentin and matrix metalloproteinase-13. The EndoG-positive WDNI cells were more sensitive to etoposide-or camptothecin-induced cell death than EndoG-negative PDI cells. Silencing of EndoG caused inhibited of SK-BR-3 WDNI cell death induced by etoposide. Human ductal carcinomas in situ expressed high levels of EndoG, while invasive medullar and ductal carcinomas had significantly decreased expression of EndoG. This correlated with decreased apoptosis as measured by TUNEL assay. Our findings suggest that the presence of EndoG in non-invasive breast cancer cells determines their sensitivity to apoptosis, which may be taken into consideration for developing the chemotherapeutic strategy for cancer treatment.

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Section: Discussionmentioning

confidence: 47%

Section: Introductionmentioning

confidence: 99%

Endonuclease G promotes cell death of non-invasive human breast cancer cells

Basnakian

Apostolov

Yin

et al. 2006

Experimental Cell Research

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“…Because it has recently been reported that cancer chemotherapeutics exert part of their pharmacological effect by triggering apoptotic cell death (Shrivastava et al, 2000), apoptosis-inducing compounds in tumor cells have become useful as lead compounds for the development of anticancer drugs. In the present study, IC101 in the range of 1 nM to 1 M induced cell death in a concentration-dependent manner with an EC 50 value of 20 nM (Fig.…”

Section: Discussionmentioning

confidence: 99%

IC101 Induces Apoptosis by Akt Dephosphorylation via an Inhibition of Heat Shock Protein 90-ATP Binding Activity Accompanied by Preventing the Interaction with Akt in L1210 Cells

Fujiwara¹,

Yamakuni²,

Ueno³

et al. 2004

J Pharmacol Exp Ther

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To find novel pharmacological tools useful for analyzing the molecular mechanism of apoptosis from natural resources, in the present study, we examined the activity of IC101, a cyclic depsipeptide isolated from Streptomyces sp. MJ202-72F3, to induce apoptosis in the L1210 cell line. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that IC101 caused a concentration-dependent cell death with a 50% effective concentration value of 20 nM. Cell shrinkage, chromatin condensation, a typical DNA ladder pattern, and up-regulation of cleaved caspase-3 expression, which were biochemical characteristics of apoptosis, were induced by IC101. It also was observed that IC101 caused a concentrationdependent dephosphorylation of Akt and Bad without affecting phosphatidylinositol-3 kinase, an upstream molecule of Akt. IC101 dephosphorylated the 90-kDa protein, as assayed by immunblotting of the cell extract by using anti-phosphotyrosine antibody. To identify the 90-kDa protein, immunoprecipitation and direct nano-flow liquid chromatography-tandem mass spectrometry (LC-MS) were performed to demonstrate that this protein was heat shock protein 90 (HSP90). Consistently, it was observed that IC101 induced the HSP90 tyrosine dephosphorylation by immunoblot analysis of immunoprecipitates with anti-HSP90 antibody using anti-phosphotyrosine antibody. IC101 caused the degradation of Raf-1, which formed a complex with HSP90. The HSP90-ATP binding also was inhibited by IC101 in a noncompetitive manner. An interaction of HSP90 with Akt was shown to be inhibited by IC101 in a concentration-dependent manner. These results suggest that IC101 dephosphorylates Akt through an inhibition of HSP90 functions, resulting in the interaction with Akt to induce apoptotic cell death of L1210 cells.Apoptosis is programmed cell death characterized by cellular changes, including cell shrinkage, membrane blebbing, and chromatin condensation. In the nuclei of apoptotic cells, DNA also is cleaved into oligonucleosomal-sized fragments (180 bp and multiples) (Kerr et al., 1972). Apoptosis can be induced by various intracellular signals, including growth factor deprivation (Araki et al., 1990) and activation of cytokine receptor (Laster et al., 1988;Nagata and Golstein, 1995). Several compounds have been reported to cause apoptosis by enhancing or suppressing these signals (Muthukkumar et al., 1995;Yao and Cooper, 1995;Stefanis et al., 1999;Fujino et al., 2002;Suk et al., 2003).Akt, a serine/threonine kinase, is the cellular homolog of the retroviral oncogene product v-Akt and the major mediator of survival signals (Franke et al., 2003;Tsuruo et al., 2003). After stimulation with growth factors and cytokines, phosphatidylinositol-3 kinase (PI3-kinase) is activated and phosphorylates phosphoinositides. The interaction of the generated phosphatidylinositol 3,4,5-trisphosphate with the pleckstrin homology domain of Akt recruits Akt to the plasma membrane, where it is phosphorylated at two key Article, publication date, and citation info...

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“…In other cells, EndoG has been recognized as a key endonuclease in the caspase-independent apoptosis (Abbott et al, 2001;Bahi et al, 2006), mitotic catastrophe (Diener et al, ;Wang et al, 2008), and necrosis (Apostolov et al, 2007a;Jiang et al, 2006). Because anticancer drugs induce apoptosis in cancer cells through endonuclease-mediated DNA fragmentation (Ploski & Aplan, 2001;Shrivastava et al, 2000), and the inhibition of endonucleases has a protective effect (Shrivastava et al, 2000), endonuclease should be considered as important mediators of cancer cell death and potential therapeutic targets for www.intechopen.com the anticancer therapy. However, delivery of endonucleases or modulation of endonuclease activity are not currently used for cancer therapy, in particular, for prostate cancer therapy.…”

Section: Cytotoxic Endonucleases In Normal Prostate and Prostate Cancmentioning

confidence: 99%