Mcl-1 Mediates Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Resistance in Human Cholangiocarcinoma Cells

Taniai, Makiko; Grambihler, Annette; Higuchi, Hajime; Werneburg, Nathan W.; Bronk, Steve F.; Farrugia, Daniel J.; Kaufmann, Scott H.; Gores, Gregory J.

doi:10.1158/0008-5472.can-03-2770

Cited by 207 publications

(202 citation statements)

References 68 publications

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“…The higher level of BCL-2 expression in this cell line is due to a characteristic abnormal chromosome 18, add(18)(q23) [27] linked to the presence of two amplicons as indicated in EGI-1 datasheet. Furthermore, a large expression of MCL-1 in TFK-1 cells, as already shown by Taniai et al [18], was observed, while …”

Section: Bcl-2 Protein Family and Hspssupporting

confidence: 73%

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The BH3-mimetic ABT-737 targets the apoptotic machinery in cholangiocarcinoma cell lines resulting in synergistic interactions with zoledronic acid

Romani

Desenzani

Morganti

et al. 2010

Cancer Chemother Pharmacol

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Purpose: In TFK-1 and EGI-1 cholangiocarcinoma cell lines zoledronic acid (ZOL) determines a S-phase block without apoptosis. Here we investigated the occurrence of apoptosis stigmata when ZOL is associated to the BH3-mimetic ABT-737. Methods:In EGI-1 and TFK-1 cholangiocarcinoma cell lines untreated or treated with ABT-737 alone or in combination with ZOL, the pro-survival proteins pattern (BCL-2, BCL-XL, MCL-1, HSP72, HSP27) was investigated by biochemical criteria along with the occurrence of mitochondrial damage evaluated by cytofluorimetric analysis using a cationic dye.Results: ABT-737 induced growth inhibition and significantly affected the colony-forming ability of both EGI-1 and TFK-1 cells. However, activated PARP-1 or/and caspase-3 cleavage (apoptosis markers) were detected only at the highest ABT-737 concentrations used. Combined treatment showed synergistic effect by converting the predominant cytostatic effect of ZOL into a cytotoxic one as shown by striking increment of mitochondrial-harmed cells along with PARP-1 activation and caspase-3 cleavage. Conclusion:The lacking of apoptosis following ZOL treatment in these cholangiocarcinoma cell lines appears to be multifactorial and could be ascribed to the large constitutive expression of prosurvival proteins. The efficacy of ZOL treatment requires a concomitant unleashing of apoptosis by using a selective BH3-mimetic as ABT-737. The rational targeting of specific components of the apoptotic pathway may appear a useful approach to improve the treatment of refractory or relapsed cholangiocarcinoma. Combined treatment could be further explored in vivo tumor model of cholangiocarcinoma

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Section: Bcl-2 Protein Family and Hspssupporting

confidence: 73%

“…Accordingly, other authors reported a direct link between overexpression of some BCL-2 protein family members (such as MCL-1) and drug resistance in cholangiocarcinoma cell lines [18].…”

Section: Introductionmentioning

confidence: 96%

The BH3-mimetic ABT-737 targets the apoptotic machinery in cholangiocarcinoma cell lines resulting in synergistic interactions with zoledronic acid

Romani

Desenzani

Morganti

et al. 2010

Cancer Chemother Pharmacol

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“…In zebrafish embryos, knockdown of zMcl1a and zMcl-1b substantially increased apoptosis triggered by ectopic expression of the Apo2L/TRAIL homolog zDL1b. Previous work suggests that in human hepatocellular carcinoma-derived cells, 32 human cholangiocarcinoma cells, 31 and NIH3T3 mouse fibroblasts, 30 Mcl-1 is a critical modulator of sensitivity to apoptosis signaling by Apo2L/TRAIL. Hence, endogenous Mcl-1 may be particularly important among prosurvival Bcl-2 family members in controlling apoptosis induction by stimuli that engage both the extrinsic and intrinsic apoptosis pathways.…”

Section: Discussionmentioning

confidence: 99%

“…[30][31][32] Thus, Mcl-1 may be a key modulator of DLinduced apoptosis in cells that require engagement of both the extrinsic and intrinsic pathways for commitment to apoptosis. Furthermore, these results indicate that endogenous zMcl-1a and zMcl-1b play an important role in curtailing apoptosis induction through the cell-intrinsic pathway in early zebrafish embryos.…”

Section: Apo2l/trailmentioning

confidence: 99%

Functional characterization of the Bcl-2 gene family in the zebrafish

Kratz

Eimon

Mukhyala³

et al. 2006

Cell Death Differ

128

155

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Members of the Bcl-2 protein family control the intrinsic apoptosis pathway. To evaluate the importance of this family in vertebrate development, we investigated it in the zebrafish (Danio rerio). We found that the zebrafish genome encodes structural and functional homologs of most mammalian Bcl-2 family members, including multi-Bcl-2-homology (BH) domain proteins and BH3-only proteins. Apoptosis induction by c-irradiation required zBax1 and zPuma, and could be prevented by overexpression of homologs of prosurvival Bcl-2 family members. Surprisingly, zebrafish Bax2 (zBax2) was homologous to mammalian Bax by sequence and synteny, yet demonstrated functional conservation with human Bak. Morpholino knockdown of both zMcl-1a and zMcl-1b revealed their critical role in early embryonic zebrafish development, and in the modulation of apoptosis activation through the extrinsic pathway. These data indicate substantial functional similarity between zebrafish and mammalian Bcl-2 family members, and establish the zebrafish as a relevant model for studying the intrinsic apoptosis pathway.

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“…Although the expression of most members of the Bcl-2 family was not altered by IL-6, a greater than two-fold increase in expression of Mcl-1 was noted (Fig 6). Mcl-1 is anti-apoptotic and has been implicated as a survival factor for cholangiocarcinoma (35)(36)(37). Moreover, Mcl-1 has been shown to be regulated by IL-6 in a variety of hepatic and other epithelial cancer cell lines such as basal cell carcinoma, gastric cancer and cervical cancer (37)(38)(39)(40)(41).…”

Section: Il-6 Increases Mcl-1 Expressionmentioning

confidence: 99%

Over-expression of interleukin-6 enhances cell survival and transformed cell growth in human malignant cholangiocytes

Meng¹,

Yamagiwa²,

Ueno³

et al. 2006

Journal of Hepatology

115

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Mcl-1 Mediates Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Resistance in Human Cholangiocarcinoma Cells

Abstract: ABSTRACT

Cited by 207 publications

References 68 publications

The BH3-mimetic ABT-737 targets the apoptotic machinery in cholangiocarcinoma cell lines resulting in synergistic interactions with zoledronic acid

The BH3-mimetic ABT-737 targets the apoptotic machinery in cholangiocarcinoma cell lines resulting in synergistic interactions with zoledronic acid

Functional characterization of the Bcl-2 gene family in the zebrafish

Over-expression of interleukin-6 enhances cell survival and transformed cell growth in human malignant cholangiocytes

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