Relationship between Suppression of E6 and E7 Virus Oncogenes and Expression of Apoptosis and Cell Cycle Genes in Cervical Cancer Culture

Хохлова, Е. В.; Шкопоров, А. Н.; Volodin, N.N.; Ефимов, Б. А.; Павлов, К. А.; Кафарская, Л. И.

doi:10.1007/s10517-010-0879-2

Cited by 4 publications

(4 citation statements)

References 10 publications

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“…Similarly, GTSE1 (G2 and S phase-expressed-1 gene) which is a key regulator of tumor cell migration and metastasis (Penna et al, 2017), was down-regulated in this study. The targeting of this gene in the cervical cancer cell line inhibits culture proliferation as seen by the previous study (Khokhlova et al, 2010).…”

Section: Discussionsupporting

confidence: 57%

The anticancer molecular mechanism of Carnosol in human cervical cancer cells: An in vitro study

Hafidh

Abdulamir

2020

APJMBB

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Carnosol, a phenolic diterpene, is one of the effective anticancer agents naturally occurring in rosemary, sage, parsley, and oregano. The chemoresistance problem increased with the routinely used chemotherapy. Therefore, the efforts to find a substitute with safe and low cost have become crucial worldwide. The current study attempts to inspect the anticancer molecular mechanisms of Carnosol on modulating up- and down- regulation of multiple genetic carcinogenesis pathways. The cytotoxicity of Carnosol on Hela cells was evaluated by MTS assay. Flow cytometry was used to assess apoptosis and cell cycle arrest. The apoptotic morphological changes were obvious by dual apoptosis assay. The differential gene expression after treatment with Carnosol was investigated by qRT-PCR. Up to 80% of the treated cells with Carnosol IC50 underwent apoptosis. Apoptosis together with cell cycle arrest in G0/G1 phase were induced significantly after treatment with Carnosol IC50. Fifteen out of nineteen genes studied were found to be remarkably up- or down- regulated after treatment with Carnosol. Six up-regulated genes (EREG, FOS-2, ID2, CRYAB, DUSP5, and TICAM2) and nine down-regulated genes (FN1, KRAS2, CCNB1-1, FEN1, MCM4, MCM5, GTSE1, CXCL1, and RALA) were recorded. These genes are candidates for future research for elucidating anticancer molecular targeted therapies, cancerous signaling and cancer development pathways in cervical cancer; moreover, elucidating the role of apoptosis, inflammation, cell proliferation, and cell differentiation in the development of cervical cancer.

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Section: Discussionsupporting

confidence: 57%

The anticancer molecular mechanism of Carnosol in human cervical cancer cells: An in vitro study

Hafidh

Abdulamir

2020

APJMBB

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“…In this study, 9-oxo-ODAs downregulated the expression of E6 and E7 in cervical cancer cells, slowed the cell cycle, and induced apoptosis. Previous reports have demonstrated that suppression of HPV oncoprotein expression causes cell cycle inhibition 31 , 32 . Our results indicated that the antitumor effects of 9-oxo-ODAs may involve the E6 and E7 pathway.…”

Section: Discussionmentioning

confidence: 99%

9-oxo-ODAs suppresses the proliferation of human cervical cancer cells through the inhibition of CDKs and HPV oncoproteins

Mogi,

Koya,

Yoshihara

et al. 2023

Sci Rep

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Mucosal human papillomavirus (HPV) subtypes 16 and 18 are causative agents of cervical cancer, a leading cause of cancer-related deaths among women worldwide. In Japan, eggplant calyx is a folk remedy used to treat common warts. 9-oxo-(10E,12E)-octadecadienoic acid, isolated from eggplant calyx, may have antitumor effects. This study investigated the antitumor effects of 9-oxo-(10E, 12Z)-octadecadienoic acid and 9-oxo-(10E,12E)-octadecadienoic acid (9-oxo-ODAs) on human cervical cancer cells. 9-oxo-ODAs suppressed the proliferation of human cervical cancer cell lines (HeLa, and SiHa) in a concentration-dependent manner (IC50 = 25–50 µM). FCM analysis revealed that 9-oxo-ODAs induced apoptosis. Transcriptome, proteomics, and enrichment analyses revealed that treatment with 9-oxo-ODAs significantly altered the cell cycle and p53 pathways and decreased cyclin-dependent kinase 1 (CDK1) protein expression. Real-time PCR analysis demonstrated that 9-oxo-ODAs reduced CDK1 mRNA expression in a concentration-dependent manner. In vitro, 9-oxo-ODAs reduced the HPV oncoprotein expression. In ex vivo human cervical cancer tissues, 9-oxo-ODAs decreased CDK1 expression and increased cleaved caspase 3, an apoptosis marker. Further, 9-oxo-ODAs showed the potential to suppressed metastatic formation and growth of cervical cancer in vivo. These findings suggest that 9-oxo-ODAs induce cell cycle arrest and apoptosis in HPV-positive human cervical cancer cells, and this process involves CDK1. Consequently, 9-oxo-ODAs may be potential therapeutic agents for cervical cancer.

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“…In this study, 9-oxo-ODAs downregulated the expression of E6 and E7 in cervical cancer cells, slowed the cell cycle, and induced apoptosis. Previous reports have demonstrated that suppression of HPV protein expression causes cell cycle inhibition 24,25 . However, the mechanisms by which 9-oxo-ODAs downregulate E6 and E7 expression remain unknown.…”

Section: Discussionmentioning

confidence: 99%

Antitumor effects of 9-oxo-10,12-ODAs on human cervical cancer cells: novel insights into CDK regulators and opportunities for cancer therapy

Mogi

Koya

Yoshihara

et al. 2022

Preprint

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Mucosal human papillomavirus (HPV) subtypes 16 and 18 are causative agents of cervical cancer, a leading cause of cancer-related deaths among women worldwide. In Japan, eggplant calyx is a folk remedy used to treat common warts. 9-oxo-(10E,12E)-octadecadienoic acid, isolated from eggplant calyx, may have antitumor effects. This study investigated the antitumor effects of 9-oxo-(10E, 12Z)-octadecadienoic acid and 9-oxo-(10E,12E)-octadecadienoic acid (9-oxo-ODAs) on human cervical cancer cells. 9-oxo-ODAs suppressed the proliferation of human cervical cancer cell lines (CasKi, HeLa, and SiHa) in a concentration-dependent manner (IC50 = 25-50uM). FCM analysis revealed that 9-oxo-ODAs induced apoptosis. Transcriptome, proteomics, and enrichment analyses revealed that treatment with 9-oxo-ODAs significantly altered the cell cycle and p53 pathways and decreased cyclin-dependent kinase 1 (CDK1) protein expression. Real-time PCR analysis demonstrated that 9-oxo-ODAs reduced CDK1 mRNA expression in a concentration-dependent manner. In vitro, 9-oxo-ODAs reduced the HPV-related protein expression. In ex vivo human cervical cancer tissues, 9-oxo-ODAs decreased CDK1 expression and increased cleaved caspase 3, an apoptosis marker. Further, 9-oxo-ODAs suppressed metastatic formation and growth of cervical cancer in vivo. These findings suggest that 9-oxo-ODAs induce cell cycle arrest and apoptosis in HPV-positive human cervical cancer cells, and this process involves CDK1. Consequently, 9-oxo-ODAs may be potential therapeutic agents for cervical cancer.

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Relationship between Suppression of E6 and E7 Virus Oncogenes and Expression of Apoptosis and Cell Cycle Genes in Cervical Cancer Culture

Cited by 4 publications

References 10 publications

The anticancer molecular mechanism of Carnosol in human cervical cancer cells: An in vitro study

The anticancer molecular mechanism of Carnosol in human cervical cancer cells: An in vitro study

9-oxo-ODAs suppresses the proliferation of human cervical cancer cells through the inhibition of CDKs and HPV oncoproteins

Antitumor effects of 9-oxo-10,12-ODAs on human cervical cancer cells: novel insights into CDK regulators and opportunities for cancer therapy

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