Dataset Information

Curcumin-Mediated Degradation of S-Phase Kinase Protein 2 Induces Cytotoxic Effects in Human Papillomavirus-Positive and Negative Squamous Carcinoma Cells.

ABSTRACT: S-phase kinase-associated protein2 (Skp2), a proto-oncoprotein, plays an important role in development and progression of human malignancies. Skp2 is frequently overexpressed in many human malignancies. It targets cell cycle progression through ubiquitin mediated degradation of G1-checkpoint CDK inhibitors-p21 (CDKN1A) and p27 (CDKN1B). We investigated the role of Skp2 and its ubiquitin-proteasome pathway in head and neck squamous cell carcinoma (HNSCC) using a panel of cell lines with and without human papillomavirus (HPV⁺, HPV^-). Treatment of HNSCC cell lines with curcumin, a natural compound isolated from rhizomes of the plant Curcuma longa, or transfection of small interfering RNA of Skp2, causes down-regulation of Skp2 with concomitant accumulation of p21 and p27 in HPV⁺, HPV^- cells. Furthermore curcumin inhibits cell viability and induces apoptosis in a dose-dependent manner. Treatment of HPV⁺ and HPV^- cells with curcumin induced apoptosis via mitochondrial pathway and activation of caspases. In addition, treatment of HPV⁺ and HPV^- cell lines with curcumin down-regulated the expression of XIAP, cIAP1, and cIAP2. Interestingly, co-treatment of HNSCC cells with curcumin and cisplatin potentiated inhibition of cell viability and apoptotic effects. Altogether, these data suggest an important function for curcumin, acting as a suppressor of oncoprotein Skp2 in squamous cell carcinoma cells in both HPV⁺ and HPV^- cells; raise the possibility that this agent may have a future therapeutic role in squamous cell carcinoma.

SUBMITTER: Khan AQ

PROVIDER: S-EPMC6176276 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Curcumin-Mediated Degradation of S-Phase Kinase Protein 2 Induces Cytotoxic Effects in Human Papillomavirus-Positive and Negative Squamous Carcinoma Cells.

Khan Abdul Q AQ Siveen Kodappully S KS Prabhu Kirti S KS Kuttikrishnan Shilpa S Akhtar Sabah S Shaar Abdullah A Raza Afsheen A Raza Afsheen A Mraiche Fatima F Dermime Said S Uddin Shahab S

Frontiers in oncology 20181002

S-phase kinase-associated protein2 (Skp2), a proto-oncoprotein, plays an important role in development and progression of human malignancies. Skp2 is frequently overexpressed in many human malignancies. It targets cell cycle progression through ubiquitin mediated degradation of G1-checkpoint CDK inhibitors-p21 (CDKN1A) and p27 (CDKN1B). We investigated the role of Skp2 and its ubiquitin-proteasome pathway in head and neck squamous cell carcinoma (HNSCC) using a panel of cell lines with and witho ...[more]

PMID: 30333956

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Project description:Vulvar squamous cell carcinoma (VSCC) is a biologically and morphologically diverse disease, consisting of human papillomavirus (HPV)-positive and -negative tumors that differ in their morphological phenotypes and associated vulvar mucosal disorders. This study analyzed the frequencies of allelic loss (loss of heterozygosity (LOH)) in HPV-positive and -negative VSCCs to identify potential targets for the study of preinvasive diseases, to determine whether HPV status influenced patterns of LOH, and to determine whether these patterns differed from HPV-positive tumors of another genital site, cervical squamous cell carcinomas (CSCC). DNA extracted from microdissected archival sections of two index tumors, one each HPV negative and positive, was analyzed for LOH at 65 chromosomal loci. Loci scoring positive with either sample were included in an analysis of 14 additional cases that were also typed for HPV. Frequencies of LOH at loci were computed in a panel of HPV-positive and -negative VSCCs. Twenty-nine loci demonstrated LOH on the initial screen and were used to screen the remaining 14 tumors. High frequencies of LOH were identified, some of which were similar to a prior karyotypic study (3p, 5q, 8p, 10q, 15q, 18q, and 22q) and others of which had not previously been described in VSCC (1q, 2q, 8q, 10p, 11p, 11q, 17p, and 21q). With the exception of 5q and 10p, there were no significant associations between frequency of LOH and HPV status in VSCC. LOH at 3p and 11q were frequent in both VSCC and CSCC; however, allelic losses at several sites, including 5q, 8q, 17p, 21q, and 22q, were much more common in VSCC. VSCCs exhibit a broad range of allelic losses irrespective of HPV status, with high frequencies of LOH on certain chromosomal arms. This suggests that despite their differences in pathogenesis, both HPV-positive and -negative VSCCs share similarities in type and range of genetic losses during their evolution. Whether the different frequencies of LOH observed between VSCC and CSCC are real or reflect differences in stage and/or tumor size remains to be determined by further comparisons. The role of these altered genetic loci in the genesis of preinvasive vulvar mucosal lesions merits additional study.

Dataset Information

Curcumin-Mediated Degradation of S-Phase Kinase Protein 2 Induces Cytotoxic Effects in Human Papillomavirus-Positive and Negative Squamous Carcinoma Cells.

Publications

Curcumin-Mediated Degradation of S-Phase Kinase Protein 2 Induces Cytotoxic Effects in Human Papillomavirus-Positive and Negative Squamous Carcinoma Cells.

Similar Datasets

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