XIAP-mediated protection of H460 lung cancer cells against cisplatin

Cheng, Yow-Jyun; Jiang, Hang-Shiang; Hsu, Shih-Lan; Lin, Li-Chiung; Wu, Chieh‐Liang; Ghanta, Vithal K.; Hsueh, Chi-Mei

doi:10.1016/j.ejphar.2009.11.003

Cited by 39 publications

(21 citation statements)

References 25 publications

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“…It has been shown that the overexpression of XIAP by adenoviral sense XIAP complementary DNA attenuated the ability of cisplatin to induce apoptosis (33). Extensive studies have shown that downregulation of XIAP using adenoviral antisense XIAP infection or siRNA increased sensitivity to cisplatin in resistant various cancer cells (13,34,35). Consistent with those results, our results first showed that downregulation of XIAP by plasmid pSi-XIAP increased sensitivity to cisplatin in resistant OS cancer cells.…”

Section: Discussionsupporting

confidence: 81%

Silencing XIAP suppresses osteosarcoma cell growth, and enhances the sensitivity of osteosarcoma cells to doxorubicin and cisplatin

et al. 2014

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Abstract. X-chromosome-linked inhibitor of apoptosis protein (XIAP) is an important member of the inhibitors of apoptosis (IAP) family. It has been shown that XIAP promotes the invasion, metastasis, growth and survival of malignant cells, and confers resistance to some chemotherapeutic drugs in various types of cancer. However, little is known regarding its detailed role in osteosarcoma (OS). In the present study, we first investigated the expression of XIAP in OS tissues, and an increased expression of XIAP in OS tissues compared to adjacent non-tumor tissue was identified. Additionally, its expression level correlated with key pathological characteristics including clinical stage, tumor size and metastasis. Subsequently, small interfering RNA (siRNA) was used to block XIAP expression to evaluate the effect of XIAP siRNA on cell proliferation, colony formation, cell cycle, apoptosis, tumorigenicity, and the combined effects of doxorubicin or cisplatin in OS cell lines (MG63 cells). Downregulation of XIAP expression using the RNA silencing approach efficiently decreased cell proliferation and colony formation, and induced cell apoptosis and cell cycle in the G0/G1 stage. In addition, this downregulation inhibited tumor growth in a nude murine model. The resuls also showed that treatment with XIAPshRNA in combination with doxorubicin or cisplatin enhanced chemosensitivity. These results suggested that XIAP may aid the diagnosis of OS and may be an effective strategy for gene therapy of this disease.

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Section: Discussionsupporting

confidence: 81%

Silencing XIAP suppresses osteosarcoma cell growth, and enhances the sensitivity of osteosarcoma cells to doxorubicin and cisplatin

et al. 2014

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“…The inhibitor of apoptosis proteins (IAPs) such as survivin and XIAP block the execution phase of apoptosis (65). Their expression in cancer cells is associated with resistance to various pro-apoptotic agents such as TGF-b (66) and TNF-a (67), TRAIL (68,69) and to chemotherapeutic drugs (60,(69)(70)(71). Some studies have shown that Akt and particularly Akt2 regulate IAP levels in cancer cells (72,73).…”

Section: Akt Isoforms In Chemoresistancementioning

confidence: 99%

Functional specificity of Akt isoforms in cancer progression

Fortier

Asselin

Cadrin

2011

BioMolecular Concepts

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Akt/PKB kinases are central mediators of cell homeostasis. There are three highly homologous Akt isoforms, Akt1/PKBα, Akt2/PKBβ and Akt3/PKBγ. Hyperactivation of Akt signaling is a key node in the progression of a variety of human cancer, by modulating tumor growth, chemoresistance and cancer cell migration, invasion and metastasis. It is now clear that, to understand the mechanisms on how Akt affects specific cancer cells, it is necessary to consider the relative importance of each of the three Akt isoforms in the altered cells. Akt1 is involved in tumor growth, cancer cell invasion and chemoresistance and is the predominant altered isoform found in various carcinomas. Akt2 is related to cancer cell invasion, metastasis and survival more than tumor induction. Most of the Akt2 alterations are observed in breast, ovarian, pancreatic and colorectal carcinomas. As Akt3 expression is limited to some tissues, its implication in tumor growth and resistance to drugs mostly occurs in melanomas, gliomas and some breast carcinomas. To explain how Akt isoforms can play different or even opposed roles, three mechanisms have been proposed: tissue-specificity expression/activation of Akt isoforms, distinct effect on same substrate as well as specific localization through the cyto-skeleton network. It is becoming clear that to develop an effective anticancer Akt inhibitor drug, it is necessary to target the specific Akt isoform which promotes the progression of the specific tumor.

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“…It was found that exposure to nicotine led to an increase in the levels of inhibitor of apoptosis proteins (IAPs) XIAP and survivin in a α3β4 nAChR dependent manner, downstream of AKT signaling (57, 66); interestingly, nicotine did not induce cIAP1 or cIAP2 (57). AKT mediated phosphorylation is known to prevent the ubiquitination and degradation of XIAP (76); reduced ubiquitination and stabilization of XIAP was observed upon nicotine stimulation, correlating with reduced apoptosis (77). Further, induction of survivin by nicotine occurred at the transcriptional level in an E2F1-dependent fashion, suggesting that exposure to nicotine can confer resistance to apoptosis through multiple mechanisms (57).…”

Section: Regulation Of Survival Pathways By Nachrs – Anti-apoptotic Ementioning

confidence: 99%

Nicotine-Mediated Cell Proliferation and Tumor Progression in Smoking-Related Cancers

Schaal

Chellappan

2014

Molecular Cancer Research

277

269

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Tobacco smoke contains multiple classes of established carcinogens including benzo(a)pyrenes, polycyclic aromatic hydrocarbons, and tobacco specific nitrosamines. Most of these compounds exert their genotoxic effects by forming DNA adducts and generation of reactive oxygen species, causing mutations in vital genes like K-Ras and p53. In addition, tobacco specific nitrosamines can activate nicotinic acetylcholine receptors (nAChRs) and to a certain extent β-Adrenergic receptors (β-ARs), promoting cell proliferation. Further, it has been demonstrated that nicotine, the major addictive component of tobacco smoke, can induce cell cycle progression, angiogenesis, and metastasis of lung and pancreatic cancers. These effects occur mainly through the α7-nAChRs, with possible contribution from the β-ARs and/or epidermal growth factor receptors (EGFRs). This review article will discuss the molecular mechanisms by which nicotine and its oncogenic derivatives such as NNK (4-methylnitrosamino)-1-(3-pyridyl)-1-butanone) and NNN (N-nitrosonornicotine) induce cell cycle progression and promote tumor growth. A variety of signaling cascades are induced by nicotine through nAChRs, including the MAPK/ERK pathway, PI3K/AKT pathway and JAK/STAT signaling. In addition, studies have shown that nAChR activation induces Src kinase in a β-arrestin-1 dependent manner, leading to the inactivation of Rb protein and resulting in the expression of E2F1-regulated proliferative genes. Such nAChR-mediated signaling events enhance the proliferation of cells and render them resistant to apoptosis induced by various agents. These observations highlight the role of nAChRs in promoting the growth and metastasis of tumors and raise the possibility of targeting them for cancer therapy.

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XIAP-mediated protection of H460 lung cancer cells against cisplatin

Cited by 39 publications

References 25 publications

Silencing XIAP suppresses osteosarcoma cell growth, and enhances the sensitivity of osteosarcoma cells to doxorubicin and cisplatin

Silencing XIAP suppresses osteosarcoma cell growth, and enhances the sensitivity of osteosarcoma cells to doxorubicin and cisplatin

Functional specificity of Akt isoforms in cancer progression

Nicotine-Mediated Cell Proliferation and Tumor Progression in Smoking-Related Cancers

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