Increase of the resistance of human cervical carcinoma cells to cisplatin by inhibition of the MEK to ERK signaling pathway partly via enhancement of anticancer drug-induced NFκB activation

Yeh, Pei Yen; Chuang, Shuang‐En; Yeh, Kun Tu; Song, Ying; Kwee, Chee; Cheng, Ann‐Lii

doi:10.1016/s0006-2952(02)00908-5

Cited by 126 publications

(81 citation statements)

References 35 publications

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“…As discussed previously, activation of MEK/ERK pathway is critical for cisplatin-induced apoptosis (Wang et al, 2000), and inhibition of MEK/ERK pathway has been suggested to be responsible for cisplatin resistance (Yeh et al, 2002). To study whether the MEK/ ERK pathway played a role in the MAD2-mediated sensitivity to cisplatin in TGCT cells, we first examined and compared the expression of MEK pathway-related proteins in two cisplatinsensitive cell lines with relatively high levels of MAD2 (NCCIT and GH) and two cisplatin-resistant cell lines with low levels of MAD2 (2102EP and 1411HP) after treatment with cisplatin.…”

Section: Increased Mad2 Expression Correlates With Sensitivity To Cismentioning

confidence: 86%

“…For example, ERK activation is reported to be necessary for cisplatin-induced apoptosis in lung cancer cells (Wang et al, 2000), cervical carcinoma cell lines (Wang et al, 2000;Yeh et al, 2002) and malignant TGCT cell lines (Schweyer et al, 2004a). In addition, inactivation of MEK/ERK by its inhibitors has been shown to prevent apoptosis in response to cisplatin leading to resistance (Wang et al, 2000;Yeh et al, 2002), although contradictory results have been reported (Hayakawa et al, 1999;Persons et al, 1999). In this study, we found that activation of the MEK/ERK pathway was associated with increased sensitivity to cisplatin-induced apoptosis in the cells with high levels of MAD2 expression (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…They, however, suggest that only ERK activation is the most important factor for cisplatin-induced apoptosis, which is consistent with the demonstration that the cisplatin-induced ERK activation contributes to regulation of p53 by phosphorylating the tumour suppressor at serine-15 . Moreover, Yeh et al (2002) have also reported that inhibition of the MEK -ERK pathway leads to cisplatin resistance in cervical carcinoma cells. Contradictory results have also been reported that activation of ERK pathway by cisplatin antagonises apoptosis in ovarian carcinoma cell lines (Persons et al, 1999).…”

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confidence: 99%

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Role of MEK/ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells

et al. 2006

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Testicular germ cell tumour (TGCT) is the most common malignancy in young males. Although most TGCTs are sensitive to cisplatin-based chemotherapy, significant numbers of TGCT patients still relapse and die each year because of the development of resistance to cisplatin. Previously, we first reported that a key regulator of the mitotic checkpoint, mitotic arrest deficient-2 (MAD2), was a mediator of cisplatin sensitivity in human cancer cells. In this study, we investigated whether MAD2 played a role in cellular sensitivity to cisplatin in TGCT cells and the underlying molecular mechanisms responsible. Using 10 TGCT cell lines, we found that increased MAD2 expression was correlated with cellular sensitivity to cisplatin, which was associated with activation of the MEK pathway. Treatment of cells expressing high levels of MAD2 with an MEK inhibitor, U0126, led to cellular protection against cisplatininduced apoptosis. Inactivation of MAD2 by transfecting a dominant-negative construct in TGCT cells with high levels of MAD2 resulted in the suppression of MEK pathway and resistance to cisplatin-induced cell death. These results support previous suggestion on the involvement of mitotic checkpoint in DNA damage response in human cancer cells and demonstrate a possible molecular mechanism responsible for the MAD2-mediated sensitivity to cisplatin in TGCT cells. Our results also suggest that downregulation of MAD2 may be an indicator for identification of TGCT cancer cells that are potentially resistant to cisplatin-based therapy.

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Section: Increased Mad2 Expression Correlates With Sensitivity To Cismentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Role of MEK/ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells

et al. 2006

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“…As MAP kinase family member ERK has been reportedly involved in the regulation of cell death, including that of cisplatintreated tumor cells, [22][23][24][25] we investigated the influence of Pt(IV) complex 8 on ERK activation in U251 cells. Complex 8 induced ERK activation in serum-starved U251 cells after 30 min of incubation, while it was also able to potentiate ERK activation in the presence of 5% FCS (Fig.…”

Section: Pt(iv) Complex-induced Tumor Cell Death Is Erk-independentmentioning

confidence: 99%

Novel platinum(IV) complexes induce rapid tumor cell death in vitro

Kaludjerović

Miljković

Momčilović³

et al. 2005

Intl Journal of Cancer

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The anticancer activity of platinum complexes has been known since the discovery of classical Pt(II)‐based drug cisplatin. However, Pt(IV) complexes have greater inertness than corresponding Pt(II) complexes, thus allowing the oral administration and reducing the toxicity associated with platinum‐based chemotherapy. Here, we describe the in vitro antitumor activity of some novel Pt(IV)‐based agents against mouse fibrosarcoma L929 cells and human astrocytoma U251 cells. The cytotoxicity of 2 Pt(IV) complexes with bidentate ethylenediamine‐N,N′‐di‐3‐propanoato esters was found to be markedly higher than that of their Pt(II) counterparts and comparable to the antitumor action of cisplatin. In contrast to cisplatin, which caused oxidative stress‐independent apoptotic cell death of tumor cells, these Pt(IV) complexes induced oxygen radical‐mediated tumor cell necrosis. Importantly, the cytotoxic action of novel Pt(IV) complexes was markedly more rapid than that of cisplatin, indicating their potential usefulness in anticancer therapy. © 2005 Wiley‐Liss, Inc.

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“…The kinases were activated following exposure of tumour cells to cisplatin, when ERK activation might be critical for cisplatin-induced apoptosis (Persons et al, 2000;Yeh et al, 2002). Furthermore, the duration of JNK-and p38 MAPK activation was demonstrated as an early key determinant of cisplatin-induced apoptosis (Sanchez-Perez et al, 1998;Benhar et al, 2001;Mansouri et al, 2003;Kusama et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Sensitisation for cisplatin-induced apoptosis by isothiocyanate E-4IB leads to signalling pathways alterations

et al. 2006

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A new synthetic isothiocyanate (ITC) derivative, ethyl 4-isothiocyanatobutanoate (E-4IB), appeared to be an effective modulator of cellular proliferation and potent inducer of apoptosis. In cooperation with cisplatin, this compound exerted synergistic effects in human ovarian carcinoma A2780 cells. In the present study we investigated in more detail E4IB-sensitisation for cisplatin-induced apoptosis. Sequential administration of both cytostatic agents led to increased intracellular platinum accumulation, glutathione level depletion and mitochondrial membrane potential dissipation. These events were accompanied with poly (ADP-ribosyl) polymerase cleavage, stimulation of caspase-3 activity, upregulation of p53, FasL and Gadd45a, cyclin B1 downregulation and an increase in mitogen-activated protein kinases JNK, ERK and p38 phosphorylation as well as PI3K level alterations. The presented results might have implications for developing new strategies aimed at therapeutic benefit of natural or synthetic ITCs in cooperation with various anticancer drugs.

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Increase of the resistance of human cervical carcinoma cells to cisplatin by inhibition of the MEK to ERK signaling pathway partly via enhancement of anticancer drug-induced NFκB activation

Cited by 126 publications

References 35 publications

Role of MEK/ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells

Role of MEK/ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells

Novel platinum(IV) complexes induce rapid tumor cell death in vitro

Sensitisation for cisplatin-induced apoptosis by isothiocyanate E-4IB leads to signalling pathways alterations

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