High-risk HPV-positive human cancer cell lines show different sensitivity to cisplatin-induced apoptosis correlated with the p21Waf1/Cip1 level

Funaoka, K.; Shindoh, Masanobu; Yamashita, Toshiharu; Fujinaga, Kei; Amemiya, Akira; Totsuka, Yasunori

doi:10.1016/s0304-3835(96)04362-5

Cited by 19 publications

(15 citation statements)

References 16 publications

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“…12,67 Nevertheless, former studies based on HPV positive CaSki and Hela cells after cisplatin treatment showed a clear p53 and p21 WAF1 protein expression leading to the hypothesis that this drug may use a p53-dependent pathway even in the presence of E6 and E7 oncoproteins. 68,69 Taken together, our data did not rule out the involvement of a p53-dependent pathway in the ST-induced apoptosis, independent of the HPV and p53 status. Indeed, it has been recently shown that under some circumstances, the wildtype p53 function of mutant p53 genes may be restored.…”

Section: Discussioncontrasting

confidence: 81%

Staurosporine-induced apoptosis of HPV positive and negative human cervical cancer cells from different points in the cell cycle

et al. 2001

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In the present study, we compare the sensitivity of CaSki and HeLa cells (HPV positive, wild-type p53) and C33A cells (HPV negative, mutated p53) to a protein kinase inhibitor, the staurosporine (ST). We show that ST can reversibly arrest the three cervical-derived cell lines, either in G1 or in G2/M. Beyond certain ST concentrations or/and over 24 h exposure, the cells underwent apoptosis. This process took place in G1 and G2/M for C33A and CaSki plus HeLa cell lines, respectively. By using an in vitro cell-free system, we demonstrated that cytoplasmic extracts from apoptotic cells were sufficient to induce hallmarks of programmed cell death on isolated nuclei. Moreover, we found that only G2/M cytoplasmic extracts from viable CaSki and HeLa cells supplemented with ST, triggered apoptosis while exclusively G1 cytoplasmic fractions from C33A cells were efficient. Our study describes a possible involvement of the HPV infection or/and p53 status in this different ST-induced apoptosis susceptibility. Cell Death and Differentiation (2001) 8, 234 ± 244.

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Section: Discussioncontrasting

confidence: 81%

Staurosporine-induced apoptosis of HPV positive and negative human cervical cancer cells from different points in the cell cycle

et al. 2001

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“…To investigate the mechanism of cisplatin-induced ATF5 expression, ATF5 mRNA expression was examined using reverse transcription-PCR in HeLa cells treated with cisplatin at different concentration. The level of ATF5 mRNA expression did not significantly change in response to cisplatin, and the level of P21 mRNA expression was significantly increased in response to cisplatin, which was consistent with a previous report (24) (Fig. 1A).…”

Section: Cisplatin Increases Atf5 Protein Expression By Inhibiting Itssupporting

confidence: 93%

Cdc34-mediated Degradation of ATF5 Is Blocked by Cisplatin

Wei¹,

Jiang²,

Liú

et al. 2008

Journal of Biological Chemistry

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ATF5, a member of activating transcription factor (ATF)/ cAMP-response element-binding protein (CREB) family of b-ZIP transcription factors, contributes to neural cell differentiation and is involved in cell apoptosis in response to cisplatin and a number of environment factors. However, the mechanisms governing the regulation of ATF5 protein during apoptosis are largely unknown. In this study we reported that ATF5 protein was a substrate of the ubiquitin-proteasome pathway. Interestingly, the ubiquitin-dependent degradation of exogenous ATF5 protein was independent of lysine residues. Instead, the addition of a large N-terminal enhanced green fluorescence protein tag increased the stability of ATF5 protein, and the free amino acid group of the N-terminal methionine of ATF5 protein was a site for ubiquitinylation, indicating that exogenous ATF5 was degraded via the ubiquitin-proteasome system through N-terminal ubiquitinylation. Furthermore, cisplatin increased ATF5 protein expression via preventing its ubiquitin-dependent degradation, which might be associated with its promoting the nucleus-to-cytoplasm translocation of E2 ubiquitin-conjugating enzyme Cdc34 and reducing the interaction between ATF5 and Cdc34. In summary, a down-regulation of proteasome-mediated degradation of ATF5 might contribute to cisplatin-induced apoptosis, providing a new mechanism of cisplatin-induced apoptosis. ATF53 transcription factor, a member of ATF/cAMP-response element-binding protein (CREB) family of b-ZIP transcription factors (1), plays a critical role in regulating cAMP response element-dependent genes and functions as an essential role in neural cell differentiation (2-4).Accumulated data from our laboratory and other investigators indicated that ATF5 functions as an apoptosis-related protein in response to a number of environment factors and DNA damage (5, 6). Interference with the function or expression of ATF5 in glioma cells leads to their death in vitro and in vivo (7), indicating that ATF5 might be an attractive target for therapeutic intervention in glioblastoma. Consistent with this, ATF5 was widely expressed in carcinomas, and interference with its function caused apoptotic cell death of neoplastic breast cell lines (8). Furthermore, ATF5 functioned as an anti-apoptotic role in an interleukin 3-dependent cell line (9). And, we have showed that ATF5 was up-regulated by cisplatin, and its overexpression increased cisplatin-induced apoptosis in HeLa cells (5), indicating the pro-apoptotic role of ATF5 in DNA damageinduced apoptosis. Previously, Pati et al. (10) showed that ATF5 interacted with E2 ubiquitin-conjugating enzyme Cdc34. Cdc34 and RAD6 had been reported to be important components of the ubiquitin-proteasome system in the nucleus which was responsible for the degradation of some transcriptional factors (11). Although the progress in ATF5-interacting partners, function, and their relation to some diseases have been made in recent years, the precise molecular mechanisms of ATF5 protein regulation during apopto...

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“…The results showed that CMT-3 significantly suppressed the proliferation of HeLa cells in a dosedependent and time-dependent manner, but was less effective when the same experiment was conducted with Siha cells (Fig. One of the possible reasons for the different sensitive natures was reported to be the upregulation of p21 Wal/Cip1 (p53 dependent) in HeLa cells [23]. In parallel with the different sensitivity to CMT-3, Siha cells were more resistant to cisplatin-mediated cytotoxicity compared with HeLa cells [22].…”

Section: Discussionmentioning

confidence: 96%

Inhibitory impacts of chemically modified tetracycline-3 and underlying mechanism in human cervical cancer cells

Zhao

Xu²,

Yang³

et al. 2013

Anti-Cancer Drugs

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Chemically modified tetracyclines (CMTs) have been rationally designed from tetracyclines. The CMTs that show the antimicrobial properties are eliminated, whereas matrix metalloproteinase inhibitory properties are retained. Interestingly, CMT-3 (COL-3, by eliminating the dimethylamino, methyl, and hydroxyl functionalities on the basic tetracycline structure), one of the CMTs, has shown strong anticancer activity. In this study, we found that CMT-3 showed dose-dependent and time-dependent cytotoxicity in HeLa and Siha cells, two human cervical cancer cell lines. HeLa cells were more sensitive to CMT-3 compared with Siha cells. The antiproliferation potential of CMT-3 was associated with the mitochondrial apoptosis pathway, increasing reactive oxygen species level, and proapoptosis protein (e.g. caspase-3) expression, but decreasing antiapoptosis protein expression (e.g. Bcl-2). N-acetylcysteine (a reactive oxygen species inhibitor) and Z-LEHD-FMK significantly reduced or blocked the apoptosis event resulting from cytotoxic effect of CMT-3. CMT-3 also induced G0/G1 phase arrest with the reduction of cell cycle regulatory protein cyclin E and the translocation of NF-κB from the cytoplasm to the nucleus. Our findings provide the important foundation for further investigation of the underlying mechanism for the anticancer activity of CMT-3 and the potential application of CMT-3 as a new therapeutic candidate for clinical cervical cancer therapy.

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High-risk HPV-positive human cancer cell lines show different sensitivity to cisplatin-induced apoptosis correlated with the p21Waf1/Cip1 level

Cited by 19 publications

References 16 publications

Staurosporine-induced apoptosis of HPV positive and negative human cervical cancer cells from different points in the cell cycle

Staurosporine-induced apoptosis of HPV positive and negative human cervical cancer cells from different points in the cell cycle

Cdc34-mediated Degradation of ATF5 Is Blocked by Cisplatin

Inhibitory impacts of chemically modified tetracycline-3 and underlying mechanism in human cervical cancer cells

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