Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway

Leu, Cheun Miin; Chang, Chung-Ming; Hu, Cheng

doi:10.1038/sj.onc.1203452

Cited by 95 publications

(78 citation statements)

References 50 publications

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“…25 However, A431 carcinoma spheroids harboring mutant p53 21 and overexpressing EGF-Rs 24 failed to respond to the same concentration of RuCl 2 (KTZ) 2 , suggesting that EGF signaling may decrease apoptosis induced by this compound. 36 Whereas A431 carcinoma monolayers show susceptibility to the C225 anti-EGF-R MAb, the emergence of resistance to such treatment has been reported. 24 In our assays, little response to C225 against EGF-R was seen in A431 spheroids.…”

Section: Discussionmentioning

confidence: 99%

Tumor apoptosis induced by ruthenium(II)‐ketoconazole is enhanced in nonsusceptible carcinoma by monoclonal antibody to EGF receptor

Anzellotti

Sánchez‐Delgado

Rieber

2004

Intl Journal of Cancer

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KTZ, originally developed as an antifungal agent, exhibits concentration-dependent inhibitory and potentiating effects on microtubule drugs like vinblastine at concentration ranges near plasma levels of KTZ attained in human subjects. 1 KTZ is a cytochrome P-450 inhibitor that inhibits adrenal steroidogenesis 2 and shows antiglucocorticoid activity. 3 KTZ synergizes with docetaxel in the treatment of hormone-dependent cancer. 4 This finding was preceded by a report that KTZ exerts a cytostatic effect on human prostate cancer cell lines resistant to microtubule-active drugs, like vinblastine and paclitaxel, and enhances the response to these drugs. 5 Among the mechanisms involved in its anticarcinoma action, it has been reported that KTZ induces apoptosis through a p53-dependent pathway 6 and induces G 0 /G 1 arrest 7 in colorectal and hepatocellular carcinoma lines. Another azole derivative which shows potentially useful antitumor activity is CTZ, recognized as a calmodulin antagonist and inhibitor of glycolysis and known to be the primary energy source in most cancer cells. 8 CTZ induced significant reduction in glycolysis and ATP levels, which led to tumor cell destruction after 3 hr. 8 There is a need to enhance the efficacy of potentially useful anticancer agents like KTZ and CTZ and to develop new compounds capable of activity against tumor cells refractory to apoptosis since the latter property usually correlates with drug resistance.Since genetic alterations involving p53 mutation frequently correlate with decreased response to cancer chemotherapy, 9,10 we investigated whether Ru(II) complexes with CTZ or KTZ 11-13 are more effective than the parent compounds at promoting cell death in tumors with such genetic changes. The reason for this study with Ru(II)-azole complexes is to expand the range of potentially useful antitumor Ru agents since an Ru(III) complex like NAMI-A, 14 -16 which may require reduction of its Ru(III) moiety to act, has shown promising anticancer activity in initial clinical trials. 15 The effects of NAMI-A are often compared to the widely known anticancer drug cisplatin, similarly based on another transition metal. 17 Interestingly, most of the Ru complexes tested to date, including NAMI-A, have not been strikingly more cytotoxic than cisplatin, the most appropriate reference control. 17 While the effect of NAMI-A on metastasis inhibition was previously described in several models, 14,15 its mechanism of action was demonstrated only recently. In vitro studies showed that 100 M NAMI-A, active on lung tumor metastases, 14 induced apoptosis of a transformed ECV304 human endothelial cell line by promoting caspase-3 activation 16 and release of mitochondrial cytochrome c, 16,18 hallmarks of cellular suicide. The mitochondrial damage induced by NAMI-A 16 is compatible with the effect of 20 -50 M CTZ, which induces glycolysis-related hexokinase detachment from mitochondria and loss of viability in B16 melanoma. 8 Since apoptosis induced by 50 M KTZ is decreased in colorectal and hepatocellu...

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Section: Discussionmentioning

confidence: 99%

Tumor apoptosis induced by ruthenium(II)‐ketoconazole is enhanced in nonsusceptible carcinoma by monoclonal antibody to EGF receptor

Anzellotti

Sánchez‐Delgado

Rieber

2004

Intl Journal of Cancer

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“…82 MAP kinase mediated pathways (either MEK/ERK or p38) are also involved in the induction of MCL1 expression in other systems. [83][84][85] An additional pathway, transduced through phosphatidylinositol 3-kinase (PI3K) and AKT, is involved in the induction of MCL1 expression by GM-CSF and IL-3 in hematopoietic progenitor cells. This latter pathway acts through a transcription factor complex that contains cAMP response element binding protein (CREB).…”

Section: Mcl1 Is Regulated Through Multiple Transcriptional and Post-mentioning

confidence: 99%

MCL1 provides a window on the role of the BCL2 family in cell proliferation, differentiation and tumorigenesis

2002

Leukemia

252

245

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The MCL1 gene (myeloid cell leukemia-1) was discovered serendipitously about a decade ago and proved to be a member of the emerging BCL2 gene family. Ongoing studies of this gene provide an interesting perspective on the role of the BCL2 family in transitions in cell phenotype. Specifically, gene products that influence cell viability as a major effect (eg MCL1, BCL2 and other family members) can act as key determinants in cell proliferation, differentiation and tumorigenesis. Although they do not have a direct role in proliferation/differentiation programs, these genes can either permit these programs to proceed or prevent them. Through such effects, the BCL2 family regulates the normal flow of cells through cycles of proliferation and along various pathways of differentiation. A model is presented suggesting that this is accomplished by sustaining or inhibiting viability at critical points in the cell lifecycle. These critical points represent windows of time during which cell fate transitions are effected. They can also be visualized as windows that open or close to promote or prevent continued progression along various cell fate pathways. The pattern of BCL2 family expression at these points allows for the proliferation differentiation, and continued viability of cell types that are needed, while aborting these processes for cells that are overabundant or no longer needed. The combined action of the various family members can therefore control the fate of cells, tissues and even the organism. This mechanism involving apoptosis-related genes is readily executable, and is poised to respond to external signals through the differential regulation of BCL2 family members. As such, it plays an important role in the maintenance of tissue homeostasis and function. Alterations that affect the BCL2 family impair the capacity to control the flow of cells through these critical points, and thereby 'leave the window open' for cell immortalization and cancer. Targeting this family may thus provide a means of inhibiting cancer development and inducing apoptosis in tumor cells. Leukemia (2002) 16, 444-454. DOI: 10.1038/sj/leu/2402416 Keywords: MCL1; BCL2; apoptosis; differentiation; hematopoiesis; cancer MCL1 was discovered based on increased expression during cell commitment to differentiation MCL1 was originally identified as a gene up-regulated early in the differentiation of a human myeloid leukemia cell line, ML-1. 1 These cells proliferate at an immature myeloblastic stage and undergo terminal differentiation to non-proliferative monocyte/macrophages upon exposure to phorbol esters such as 12-0-tetradecanoylphorbol 13-acetate (TPA). Commitment to differentiation occurs rapidly -within a window of several hours -upon the application of TPA to growth-arrested cells. 2 The 'commitment window' precedes phenotypic differentiation, which proceeds over the next several days. ML-1 cells that have passed through the commitment window do not difCorrespondence: RW Craig, Department of Pharmacology and Toxicology, Dartmouth Medic...

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“…To test whether IL-6 could serve as a survival factor for CE48T/VGH, staurosporine (ST), a wide-spectrum protein kinase inhibitor, was used to induce apoptosis (Leu et al, 2000) and the protective effect of IL-6 was examined. While 2.6% of CE48T/VGH underwent apoptosis under SF conditions, only 0.6% of the cells showed micronucleated morphology in the presence of IL-6 (Figure 3a).…”

Section: Il-6 Prevents Apoptosis In Ce48t/vgh Cellsmentioning

confidence: 99%

“…Detection of micronucleation by fluorescence microscopy was performed as described previously (Leu et al, 2000). In brief, 7.5 Â 10 4 cells were seeded into 24-well plates in 5% FCScontaining DMEM.…”

Section: Apoptosis Assaysmentioning

confidence: 99%

Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen-activated protein kinase pathways

Wong²,

et al. 2003

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The production of interleukin-6 (IL-6) has been discovered in a variety of human tumors. Here we report the expression of IL-6, IL-6 receptor a (IL-6Ra), and gp130 in human esophageal carcinoma tissues. We further demonstrate that IL-6 protects an esophageal carcinoma cell line CE48T/VGH from apoptosis induced by staurosporine. IL-6 stimulation induced a rapid phosphorylation of gp130 and STAT3, and a dominant-negative STAT3 completely abolished the antiapoptotic effect. IL-6 also activated ERK 1/2 in CE48T/VGH cells. Inhibition of the ERK activation by PD98059 and transfection of a dominant-negative ERK2 completely blocked the protection of IL-6 against apoptosis. Thus, both STAT and MAP kinase pathways are responsible for the IL-6-delivered survival signal in human esophageal carcinoma cells. In contrast, PI3-K inhibitors only partially attenuated the effect of IL-6, suggesting that PI3-K does not play a major role in the antiapoptotic signal of IL-6 in our system. To investigate whether IL-6 could induce the production of antiapoptotic molecules, proteins of the Bcl-2 family were measured. While Bcl-2, Bcl-x L, , and Bax were not affected, Mcl-1 was induced by IL-6 in human esophageal carcinoma cells. Our results suggest that IL-6 may contribute to the progression of esophageal cancers in an autocrine or paracrine manner.

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Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway

Cited by 95 publications

References 50 publications

Tumor apoptosis induced by ruthenium(II)‐ketoconazole is enhanced in nonsusceptible carcinoma by monoclonal antibody to EGF receptor

Tumor apoptosis induced by ruthenium(II)‐ketoconazole is enhanced in nonsusceptible carcinoma by monoclonal antibody to EGF receptor

MCL1 provides a window on the role of the BCL2 family in cell proliferation, differentiation and tumorigenesis

Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen-activated protein kinase pathways

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