Alpha-linolenic acid regulates Cox2/VEGF/MAP kinase pathway and decreases the expression of HPV oncoproteins E6/E7 through restoration of p53 and Rb expression in human cervical cancer cell lines

Deshpande, Rashmi; Mansara, Prakash; Kaul-Ghanekar, Ruchika

doi:10.1007/s13277-015-4170-z

Cited by 34 publications

(30 citation statements)

References 48 publications

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“…Therefore, it may be hypothesized that COX-2 has potential as a prognostic biomarker for breast cancer. Previous studies have reported that COX-2 was upregulated and associated with tumor invasiveness and clinical outcome in numerous types of human cancer (27)(28)(29)(30). In the present study, a correlation was revealed between high COX-2 expression and poor differentiation status (P<0.05).…”

Section: Discussionsupporting

confidence: 69%

EpCAM and COX-2 expression are positively correlated in human breast cancer

Gao

Sun

et al. 2017

Molecular Medicine Reports

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Upregulation of the epithelial cell adhesion molecule (EpCAM) is involved in tumor progression. Cyclooxygenase (COX)‑2 is the key enzyme catalyzing prostaglandin synthesis and is involved in breast cancer progression and metastasis. However, the prognostic value of EpCAM and its putative correlation with COX‑2 in breast cancer have yet to be elucidated. The aim of the present study was to assess the clinical relevance of the relationship between EpCAM and COX‑2, via examining the putative correlation between EpCAM and COX‑2 expression in various types of human breast cancer. A total of 134 breast cancer tissue samples was examined in the present study. Immunohistochemistry approach was used to detect EpCAM and COX‑2 expression in the tissue microarrays. Spearman's correlation analysis was performed to evaluate the correlation between the protein expression and clinicopathological parameters present in patients with various tumor subtypes, with the aim to potentially establish a relationship between EpCAM/COX‑2 and clinical prognosis. Expression of EpCAM and COX‑2 was revealed to be associated with tumor progression, and poor prognosis in breast cancer. The present findings demonstrated that EpCAM was involved in the regulation of COX‑2 expression, and a positive correlation between the proteins was associated with poor prognosis in patients with breast cancer. The present results suggest that EpCAM and COX‑2 may have potential as prognostic biomarkers in the diagnosis and treatment of patients with breast cancer.

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Section: Discussionsupporting

confidence: 69%

EpCAM and COX-2 expression are positively correlated in human breast cancer

Gao

Sun

et al. 2017

Molecular Medicine Reports

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“…The oncoproteins E6 and E7 of hrHPV, especially in HPV16/18, have been proved to play critical roles in cervical cancer through different pathways, including inactivating the products of tumor suppressor genes p53 and Rb, respectively (39,40). RASSf1A can induce cell cycle arrest by engaging the Rb family cell cycle checkpoint and the RASSF1A-induced cell cycle arrest can be relieved by the downstream activators of the G1/S-phase transition (cyclin A and E7) (13,24,41), revealing that E6, E7 may participate in the pathogenetic mechanisms of RASSF1A.…”

Section: Discussionmentioning

confidence: 99%

HPV16 oncogenes E6 or/and E7 may influence the methylation status of RASSFIA gene promoter region in cervical cancer cell line HT-3

Yin

Wang

Wang³

et al. 2017

Oncology Reports

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Both human papillomavirus (HPV) infection and the aberrant Ras associated domain family gene 1A (RASSF1A) promoter methylation status participate in the pathogenesis of cervical cancer. Some studies suggest that E6, and E7 are involved in the pathogenetic mechanisms of RASSF1A. We mainly explored a possible involvement of HPV16 oncogenes E6 or/and E7 in RASSF1A promoter methylation status and possible roles of RASSF1A gene methylation in cervical cancer. Bisulfite genomic sequencing (BGS) PCR combined with TA clone, methylation-specific PCR (MSP) were used to analyze methylation status of the RASSF1A gene promoter in HPV16/18-positive and HPV-negative cervical cancer cell lines; ectopically expressed HPV16 E6, E7 and E6/E7 cervical cancer cell lines; normal cervical and cervical cancer tissues. The mRNA and protein expression of RASSF1A was detected by RT-PCR and western blotting. Re-expression and downregulated promoter methylation status were detected in the ectopically expressed HPV16 E6 and E7 cervical cancer cell line HT-3. The methylation status and expression of RASSF1A could be downregulated or reactivated by 5-Aza-dc in HT-3 and C33A cells. Additionally, statistics showed significant hypermethylation of RASSF1A in cervical cancer samples compared to that in normal cervical samples (P<0.05). The false negative rate (FNR) was 6.25% by HC2 method, when reconfirmed by HPV detection combining the MY09/11, GP5+/6+ and SPF1/2 methods. The ectopic expression of HPV16 E6 and/or E7 may be involved in aberrant methylation and expression of the RASSF1A gene. RASSF1A gene expression could be regulated by its promoter methylation status. Additionally, the false negativity of the HPV detection may contribute to the uncertain relationship between HPV infection and aberrant RASSF1A promoter methylation.

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“…It has been reported that COX2 is upregulated in different cancers and its elevation results in a poor prognosis such as axillary node and bone metastases, and chemotherapy resistance [ 22 – 26 ]. Inhibition of COX2 can act in a concerted way with improved therapeutic potential in invasive breast cancer, non small cell lung cancer, bladder cancer and cervical cancer [ 18 , 27 – 29 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of COX2 enhances the chemosensitivity of dichloroacetate in cervical cancer cells

Xiong

et al. 2017

Oncotarget

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Dichloroacetate (DCA), a traditional mitochondria-targeting agent, has shown promising prospect as a sensitizer in fighting against malignancies including cervical cancer. But it is unclear about the effect of DCA alone on cervical tumor. Moreover, previous reports have demonstrated that the increased cyclooxygenase-2 (COX2) expression is associated with chemoresistance and poor prognosis of cervical cancer. However, it is still unknown whether COX2 can affect the sensitivity of DCA in cervical cancer cells. In this study, we found that cervical cancer cells were insensitive to DCA. Furthermore, we for the first time revealed that DCA could upregulate COX2 which impeded the chemosensitivity of DCA in cervical cancer cells. Mechanistic study showed that DCA reduced the level of RNA binding protein quaking (QKI), leading to the decay suppression of COX2 mRNA and the subsequent elevation of COX2 protein. Inhibition of COX2 using celecoxib could sensitize DCA in repressing the growth of cervical cancer cells both in vitro and in vivo. These results indicate that COX2 is a novel resistance factor of DCA, and combination of celecoxib with DCA may be beneficial to the treatment of cervical cancer.

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Alpha-linolenic acid regulates Cox2/VEGF/MAP kinase pathway and decreases the expression of HPV oncoproteins E6/E7 through restoration of p53 and Rb expression in human cervical cancer cell lines

Cited by 34 publications

References 48 publications

EpCAM and COX-2 expression are positively correlated in human breast cancer

EpCAM and COX-2 expression are positively correlated in human breast cancer

HPV16 oncogenes E6 or/and E7 may influence the methylation status of RASSFIA gene promoter region in cervical cancer cell line HT-3

Inhibition of COX2 enhances the chemosensitivity of dichloroacetate in cervical cancer cells

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