Inhibitors of apoptosis proteins in human cervical cancer

Espinosa, Magali; Cantú, David; Herrera, Norma Estela González; Lopez, Carlos M; Garza, Jaime G. De La; Maldonado, Vilma; Meléndez-Zajgla, Jorge

doi:10.1186/1471-2407-6-45

Cited by 39 publications

(36 citation statements)

References 32 publications

(29 reference statements)

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“…Because survivin is not present in healthy tissue but is expressed in neoplastic tissue and involved in tumor progression, it has been investigated as a potential target for antineoplastic therapy. 14 In the present study, moderate to strong survivin expression was detected in 70% of the samples in the CIN-2 group, 66.7% of the samples in the CIN-3 group, and 74.6% of the samples in the ICC group, which is in agreement with the findings of Espinosa et al 15 Specific studies of telomerase in cervical cancer have suggested that telomerase activity may be a definitive and reliable test for malignancy. The detection of human telomerase RNA seems to be in good agreement with the levels of telomerase activity detected by telomeric repeat amplification protocols.…”

Section: Discussionsupporting

confidence: 95%

Survivin and Telomerase Expression in the Uterine Cervix of Women With Human Papillomavirus-Induced Lesions

Barbosa¹,

Silva

Correa³

et al. 2011

Int J Gynecol Cancer

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The results suggest that mechanisms that promote both cell proliferation (telomerase activity) and cell survival (survivin expression) are active in cervical cancer and its precursor lesions. There was a negative correlation between survivin expression and the number of PCR cycles necessary to detect telomerase activity in the total sample, achieving statistical significance in patients in the CIN-3 group.

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Section: Discussionsupporting

confidence: 95%

Survivin and Telomerase Expression in the Uterine Cervix of Women With Human Papillomavirus-Induced Lesions

Barbosa¹,

Silva

Correa³

et al. 2011

Int J Gynecol Cancer

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“…It is conceivable that the overexpression of IAPs may be linked with tumor prognosis and drug resistance to chemotherapy (10). Among studies that associate IAPs with the clinical outcome, XIAP expression has been shown to have an adverse prognostic significance for patients with lung cancer (11), mesothelioma (12), and myeloid leukemias (13), but not for cervical cancer (14). In chemoresistance studies, expressions of XIAP and cIAP2 in pancreatic and prostate cancer have been shown to be associated with resistance to cisplatin and other anticancer drugs (15)(16)(17).…”

mentioning

confidence: 99%

cIAP2 Upregulated by E6 Oncoprotein via Epidermal Growth Factor Receptor/Phosphatidylinositol 3-Kinase/AKT Pathway Confers Resistance to Cisplatin in Human Papillomavirus 16/18–Infected Lung Cancer

Cheng

et al. 2010

Clinical Cancer Research

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Purpose: Inhibitors of antiapoptosis protein (IAP) have been implicated in the resistance to cisplatin. Therefore, verifying which pathway is involved in cIAP2 upregulation may be helpful in finding a feasible pathway inhibitor to increase the chemotherapeutic efficacy in human papillomavirus (HPV)-infected lung cancer.Experimental Design: Specific inhibitors of different pathways were used to verify which pathway is involved in cIAP2 transcription. cIAP2 promoter fragments with various deletions and/or mutations were constructed by site-directed mutagenesis. cIAP2, epidermal growth factor receptor (EGFR), and phospho-AKT (p-AKT) expressions in 136 lung tumors were evaluated by immunohistochemistry.Results: Our data show that two NF-κB (−209 to −200 and −146 to −137) and one CREB (cyclic AMPresponsive element binding protein; −52 to −42) binding sites in cIAP2 promoter region were responsible for cIAP2 upregulated by E6 in TL-1 cells. Moreover, CREB was phosphorylated by EGFR/phosphatidylinositol 3-kinase (PI3K) pathway. To test the involvement of cIAP2 on cisplatin resistance, IC 50 was lowered to 8.6 μmol/L in TL-1 cells with cIAP2 short hairpin RNA (shRNA) transfection and compared with 39.7 μmol/L in TL-1 cells with nonspecific shRNA. Pretreatment with EGFR or PI3K inhibitor in TL-1 cells diminished the resistance to cisplatin. Among the tumor groups, cIAP2 expression correlated significantly with HPV16/18 E6, EGFR, and p-AKT. We followed up 46 of 136 patients who had tumor recurrence and/or metastasis and underwent chemotherapy. Tumors with cIAP2-positive immunostaining were associated with a poorer tumor response to chemotherapy compared with those with negative immunostaining.Conclusions: cIAP2 upregulated by E6 via EGFR/PI3K/AKT cascades may contribute to cisplatin resistance, revealing that the EGFR or PI3K inhibitor combined with cisplatin may improve the chemotherapeutic efficacy in HPV-infected lung cancer.

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“…AIF is a caspase-independent apoptosis effector that can be released from the mitochondria into the cytosol (27)(28)(29), and is believed to be involved in caspase-independent cell death (17,18). Correspondingly, our Western blot analysis revealed that treatment of HA22T cells with 0, 50, 100, 150, 200 and 250 µg/ml YBBEs for 24 h resulted in increased AIF production (Fig.…”

Section: Discussionmentioning

confidence: 52%

Zanthoxylum avicennae extracts induce cell apoptosis through protein phosphatase 2A activation in HA22T human hepatocellular carcinoma cells and block tumor growth in xenografted nude mice

et al. 2011

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Abstract. The use of herbs as alternative cancer therapies has attracted a great deal of attention owing to their lower toxicity. Whether Zanthoxylum avicennae (Ying Bu Bo, YBB) induces liver cancer cell apoptosis remains unclear. In this study, we investigated the effect of YBB extracts (YBBEs) on HA22T human hepatocellular carcinoma cells in vitro and in an in vivo mouse xenograft model. HA22T cells were treated with different concentrations of YBBEs and analyzed with Western blot analysis, TUNEL, JC-1 staining and siRNA transfection assays. Additionally, the HA22T-implanted xenograft nude mice model was applied to confirm the cellular effects. YBBEs-induced apoptosis, up-regulated death receptor apoptotic pathway markers as well as mitochondrial proteins, and suppressed the survival proteins in a dose-dependent manner. Pro-survival Bcl-2 family proteins were inhibited and the proapoptotic ones were increased. Protein phosphatase 2A (PP2A) siRNA or okadaic acid reversed the YBBEs effects, confirming the role of PP2A in YBBEs-induced HA22T apoptosis. All our experimental evidence indicates that YBBEs significantly promote HA22T apoptosis and reduce tumor sizes in xenograft nude mice via PP2A in a dose-dependent manner.

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Inhibitors of apoptosis proteins in human cervical cancer

Abstract: Background: It has been shown that IAPs, in particular XIAP, survivin and c-IAP1, are overexpressed in several malignancies. In the present study we investigate the expression of c-IAP1, c-IAP2, XIAP and survivin and its isoforms in cervical cancer.

Cited by 39 publications

References 32 publications

Survivin and Telomerase Expression in the Uterine Cervix of Women With Human Papillomavirus-Induced Lesions

Survivin and Telomerase Expression in the Uterine Cervix of Women With Human Papillomavirus-Induced Lesions

cIAP2 Upregulated by E6 Oncoprotein via Epidermal Growth Factor Receptor/Phosphatidylinositol 3-Kinase/AKT Pathway Confers Resistance to Cisplatin in Human Papillomavirus 16/18–Infected Lung Cancer

Zanthoxylum avicennae extracts induce cell apoptosis through protein phosphatase 2A activation in HA22T human hepatocellular carcinoma cells and block tumor growth in xenografted nude mice

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