Bcl-xL confers multi-drug resistance in several squamous cell carcinoma cell lines

Noutomi, T.; Chiba, Hiroshige; Itoh, Mizue; Toyota, Hiroko; Mizuguchi, Junichiro

doi:10.1016/s1368-8375(00)00098-1

Cited by 38 publications

(32 citation statements)

References 31 publications

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“…Cells were cultured with or without the indicated concentrations of TRAIL for various times, and cell survival was estimated using a WST-8 assay kit (Dojndo Laboratories, Kumamoto, Japan), as previously described (20).…”

Section: Methodsmentioning

confidence: 99%

“…Western blotting was carried out as previously described (20). The antibodies (Abs) used here included anti-phospho-specific JNKs, total anti-JNK1, and actin (Santa Cruz Biotechnology, Santa Cruz, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…To explore the requirement for JNK1 activation in the TRAIL-induced cytotoxicity in SCC cells, a line of TRAIL-sensitive MIT6 cells overexpressing dnJNK1 was established using the procedure as previously described (20,21). One (DN12) of several clones was demonstrated to express exogenous dnJNK1 (p47) as well as a major endogenous form of JNK1 (p46) (Fig.…”

Section: Establishment Of Mit6 Cell Lines Overexpressing Dominantnegamentioning

confidence: 99%

“…We previously established several OSCC lines derived from primary lesions and their metastatic counterparts (20). The OSCC line MIT6 derived from primary OSCC was substantially more sensitive to chemotherapeutic agents than its metastatic counterpart MIL6.…”

Section: Introductionmentioning

confidence: 99%

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Tumor necrosis factor-related apoptosis-inducing ligand induces apoptotic cell death through c-Jun NH2-terminal kinase activation in squamous cell carcinoma cells

Noutomi

Itoh²,

Toyota³

et al. 2009

Oncol Rep

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Abstract. Tumor necrosis factor (TNF)-related apoptosisinducing ligand (TRAIL) induces apoptosis in MIT6 cells derived from primary oral squamous cell carcinoma (OSCC), whereas it does not induce apoptosis in MIL6 cells derived from metastases. The present studies were performed to examine whether activation of c-Jun NH 2 -terminal kinase (JNK) is implicated in the differential sensitivity to TRAILinduced apoptosis. The TRAIL-induced JNK activation in MIT6 cells was stronger than in MIL6 cells, as assessed by Western blotting using antibodies specific for phospho-JNK. To evaluate the role of JNK1 in TRAIL-induced cell death, one clone expressing the dominant-negative form of JNK1 (dnJNK1) was established. The dnJNK1-expressing cells and MIL6 cells expressed TRAIL protein at levels similar to or even greater than MIT6 cells did. When cell death was assessed by annexin V staining and mitochondrial membrane potential, kinetic studies demonstrated that the dnJNK1-expressing cells were substantially more resistant to 100 ng/ml TRAIL, comparable to MIL6 cells, at 36 and 48 h after stimulation. Collectively, the primary OSCC cell line, MIT6, is sensitive to TRAIL but its metastatic line MIL6 is resistant to TRAIL exposure. Thus, the underlying molecular mechanism of TRAIL-induced cell death involves JNK activation. These results suggest that the acquisition of TRAIL resistance provides some metastatic capacity to primary tumors.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Establishment Of Mit6 Cell Lines Overexpressing Dominantnegamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Tumor necrosis factor-related apoptosis-inducing ligand induces apoptotic cell death through c-Jun NH2-terminal kinase activation in squamous cell carcinoma cells

Noutomi

Itoh²,

Toyota³

et al. 2009

Oncol Rep

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“…Apoptosis regulating proteins involved in chemotherapeutic resistance have previously been observed, both in intrinsic (non-receptor mediated) and extrinsic (receptor mediated) apoptosis pathways [10][11][12][13] . Upregulation of anti-apoptotic molecules in the intrinsic pathway, such as Bcl-2 and Bcl-X L [14][15][16] , deficiency of pro-apoptotic p53 17 or inactivation of caspase-3 18 can significantly increase drug resistance. On the other hand, down-regulation or loss function of CD95/Fas in the extrinsic pathway contributes to chemoresistance 19 .…”

Section: Persistent Infection Of Human Papilloma Virus (Hpv)mentioning

confidence: 99%

Untitled

Aungsumart¹,

Vaeteewoottacharn²,

Chamutpong³

et al. 2007

ScienceAsia

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Alteration of the apoptosis pathway, as well as the presence of human papilloma virus (HPV), has been linked to the proliferative capacity and drug resistant phenotype of SiHa cervical cancer. We investigated the roles of E6 and E7 HPV oncoproteins in the expression of apoptosis regulating genes in cervical cancer cells that contain the characteristics of apoptosis resistance, and also their correlation with resistance to various apoptosis inducing agents. The expression of the sets of apoptosis regulating genes in both extrinsic (receptor) and intrinsic (non-receptor) pathways were monitored in parental SiHa and multi-drug resistant SiHa (SiHaR) cell lines by RNase protection assay and RT-PCR. An increase in gene expression of intrinsic pathway anti-apoptotic protein Bcl-X L was seen, both at the mRNA and protein levels, in SiHaR compared with SiHa cells, whereas the expression of the genes involved in the extrinsic pathway remained unchanged. SiHaR cells also expressed higher levels of E6 and E7 than did SiHa. Caspase 3 activity was lower in SiHaR compared with that in SiHa cells. A colony formation assay demonstrated enhanced resistance of SiHaR cells to several types of apoptosis inducing agents, including etoposide, doxorubicin, cisplatin, and γ-radiation. Transfection of HPV-negative C33a cells with HPV oncogenes, E7 in particular, induced transcription of Bcl-X L , supporting the role of HPV oncoproteins in affording chemo-radio resistance in cervical cancer.

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Role of c‐Jun N‐terminal kinase activation in apoptosis induced by removal of the growth factors

Ning

2015

Cell Biology International

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Apoptosis plays a crucial role for generation of lymphocyte repertoire, clonal contraction, and elimination of virus-infected cells. Since IL-3-dependent pro-B cell line Baf-3 resulted in rapid induction of apoptotic cell death upon IL-3 withdrawal, it would by very valuable for analysis of apoptosis induction by growth factor deprivation. First, we confirmed that Baf-3 cells underwent loss of mitochondrial membrane potential (ΔΨm) and apoptosis in a time-dependent manner when they were cultured in the RPMI-1640 medium without IL-3. Induction of apoptosis and loss of ΔΨm was determined by DiOC6 and annexin V staining method using flow cytometer, respectively. Deprivation of IL-3 induced upregulation of proapoptotic molecule Bax, in conjunction with slight down-regulation of anti-apoptotic molecule Bcl-xL, which was assessed by Western blotting. Since Bcl-xL-overexpressing Baf-3 cells showed some resistance to IL-3-deprivation, Bcl-xL prevents apoptosis induced by IL-3 withdrawal. Finally, a sustained JNK1 activation was observed prior to induction of apoptosis upon IL-3 deprivation. Dominat-negative form of JNK1 and JNK inhibitor sp600125 partially inhibit the apoptosis upon IL-3 deprivation, suggesting that a sustained JNK1 activation was involved in the induction of apoptosis. Together, IL-3 deprivation of IL-3-dependent cell line Baf-3 induces a sustained JNK1 activation, followed by a decline of the ratio of Bcl-xL to Bax, leading to loss of DCm, and finally apoptosis.

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Bcl-xL confers multi-drug resistance in several squamous cell carcinoma cell lines

Cited by 38 publications

References 31 publications

Tumor necrosis factor-related apoptosis-inducing ligand induces apoptotic cell death through c-Jun NH2-terminal kinase activation in squamous cell carcinoma cells

Tumor necrosis factor-related apoptosis-inducing ligand induces apoptotic cell death through c-Jun NH2-terminal kinase activation in squamous cell carcinoma cells

Untitled

Role of c‐Jun N‐terminal kinase activation in apoptosis induced by removal of the growth factors

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