Cytochrome P450 1B1 Overexpression in Cervical Cancers: Cross-sectional Study

Background Current standard treatments for patients with recurrent cervical cancer are not very effective and are associated with severe toxicity. Recently, the rational approach for the discovery of new therapies for cervical cancer is based on the alterations in the molecular biology of cancer cells. One of the emerging molecular changes in cancer cells is the aberrant expression of cytochrome P450 1B1 (CYP1B1). This unique enzyme has been reported to be selectively overexpressed in several cancers. Objective The aim of this study was to examine CYP1B1 expression in cervical cancers and to assess the enzyme’s relationship with several clinicopathological features. Methods Immunohistochemistry was performed to examine CYP1B1 expression in 100 patient samples with cervical cancer and 10 patient samples with normal healthy cervical tissues. Results CYP1B1 was expressed in the majority of the cervical cancer samples (91/100, 91.0%) but not in normal healthy cervical samples. The difference in the expression of CYP1B1 between healthy and tumorous cervical tissues was significant (P=.01). Moreover, the frequency of CYP1B1 expression was found to be significantly higher in patients with advanced grades of the disease (P=.03) and in patients having metastasis to the lymph nodes (P=.01). Surprisingly, there was a significantly higher expression of CYP1B1 in patients with a high prevalence of human papilloma virus 16/18 (P=.04). Conclusions The differential profile of CYP1B1 expression between cervical cancer tissues and normal cervical tissues suggests that CYP1B1 may be used as a target for future therapeutic exploitations.

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Cytochrome P450 1B1 Overexpression in Cervical Cancers: Cross-sectional Study (Preprint)

10.2196/preprints.31150 ◽

2021 ◽

Author(s):

Fatemah O F O Alshammari ◽

Yousef M Al-saraireh ◽

Ahmed M M Youssef ◽

Yahya M Al-Sarayra ◽

Hamzeh Mohammad Alrawashdeh

Keyword(s):

Cervical Cancer ◽

Cytochrome P450 ◽

Cancer Cells ◽

Rational Approach ◽

Severe Toxicity ◽

Cross Sectional ◽

Aberrant Expression ◽

Recurrent Cervical Cancer ◽

Cervical Cancers ◽

Cytochrome P450 1B1

BACKGROUND Current standard treatments for patients with recurrent cervical cancer are not very effective and are associated with severe toxicity. Recently, the rational approach for the discovery of new therapies for cervical cancer is based on the alterations in the molecular biology of cancer cells. One of the emerging molecular changes in cancer cells is the aberrant expression of cytochrome P450 1B1 (CYP1B1). This unique enzyme has been reported to be selectively overexpressed in several cancers. OBJECTIVE The aim of this study was to examine CYP1B1 expression in cervical cancers and to assess the enzyme’s relationship with several clinicopathological features. METHODS Immunohistochemistry was performed to examine CYP1B1 expression in 100 patient samples with cervical cancer and 10 patient samples with normal healthy cervical tissues. RESULTS CYP1B1 was expressed in the majority of the cervical cancer samples (91/100, 91.0%) but not in normal healthy cervical samples. The difference in the expression of CYP1B1 between healthy and tumorous cervical tissues was significant (P=.01). Moreover, the frequency of CYP1B1 expression was found to be significantly higher in patients with advanced grades of the disease (P=.03) and in patients having metastasis to the lymph nodes (P=.01). Surprisingly, there was a significantly higher expression of CYP1B1 in patients with a high prevalence of human papilloma virus 16/18 (P=.04). CONCLUSIONS The differential profile of CYP1B1 expression between cervical cancer tissues and normal cervical tissues suggests that CYP1B1 may be used as a target for future therapeutic exploitations.

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Glycyrrhiza glabra extract and quercetin reverses cisplatin resistance in triple-negative MDA-MB-468 breast cancer cells via inhibition of cytochrome P450 1B1 enzyme

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2017.11.013 ◽

2017 ◽

Vol 27 (24) ◽

pp. 5400-5403 ◽

Cited By ~ 12

Author(s):

Rajni Sharma ◽

Linda Gatchie ◽

Ibidapo S. Williams ◽

Shreyans K. Jain ◽

Ram A. Vishwakarma ◽

...

Keyword(s):

Breast Cancer ◽

Cytochrome P450 ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Triple Negative ◽

Cisplatin Resistance ◽

Glycyrrhiza Glabra ◽

Cytochrome P450 1B1

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The potential oncogenic and MLN4924-resistant effects of CSN5 on cervical cancer cells

Cancer Cell International ◽

10.1186/s12935-021-02078-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Huilin Zhang ◽

Ping He ◽

Qing Zhou ◽

Yan Lu ◽

Bingjian Lu

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Cell ◽

Cervical Cancer Cell ◽

Cervical Cancers ◽

Cervical Cancer Cells

Abstract Background CSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet. Methods Data from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 and clinical relevance in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR–CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. The biological behaviors were analyzed by CCK8, clone formation assay, 3-D spheroid generation assay and cell cycle assay. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. MLN4924 was given in Siha and Hela with CSN5 overexpression. Results We found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells. Conclusions Our findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

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The Potential Oncogenic and MLN4924-Resistant Effects of CSN5 on Cervical Cancer Cells

10.21203/rs.3.rs-550782/v1 ◽

2021 ◽

Author(s):

Huilin Zhang ◽

Ping He ◽

Qing Zhou ◽

Yan Lu ◽

Bingjian Lu

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Cell ◽

Cervical Cancer Cell ◽

Cervical Cancers ◽

Cervical Cancer Cells

Abstract BackgroundsCSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet.MethodsData from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR-CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. CCK8, clone formation assay and cell cycle assay were also employed. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. Moreover, MLN4924 was applied in Siha and Hela with CSN5 overexpression.ResultsWe found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells.ConclusionsOur findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

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Signaling Pathways in Cervical Cancer Chemoresistance: Are microRNAs and Long-Noncoding RNAs the Main Culprits?

10.20944/preprints202004.0294.v1 ◽

2020 ◽

Author(s):

Seyyed Reza Mousavi ◽

Nima Hemmat ◽

Hossein Bannazadeh Baghi ◽

Afshin Derakhshani ◽

Stefania Tommasi ◽

...

Keyword(s):

Cervical Cancer ◽

Drug Resistance ◽

Signaling Pathways ◽

Molecular Mechanisms ◽

Bioinformatic Analysis ◽

Aberrant Expression ◽

Recurrent Cervical Cancer ◽

Response To Chemotherapy ◽

Wide Range ◽

Non Coding Rnas

Cervical cancer is known as one of the most important cancers in women worldwide. Chemotherapy is a standard treatment for advanced/recurrent cervical cancer in which the prognosis of the disease is really poor and the 1-year survival chance in these patients is maximally 20%. However, resistance to anticancer drugs is a major problem in treating cancer. Cervical cancer stem cells are considered as a fundamental cause of chemo and radio-resistance and also relapse after primary successful treatment. Signaling pathways include a wide range of molecular mechanisms contribute to drug resistance. Recently, microRNAs (miRNAs) are announced as a group of molecular biomarkers involving in response to chemotherapy in cancer patients. As the miRNAs, there are some long non-coding RNAs (LncRNAs) which their aberrant expression is considered as a biomarker for monitoring chemoresistance. In this review, we summarized current reports about the involvement of signaling pathways during chemoresistance in cervical cancer. Then, genes that have been demonstrated their involvement during drug resistance in cervical cancer were tabulated. Further, miRNAs that have been reported as biomarkers during treatment are listed. By bioinformatic analysis, we predictedmiR-335-5p and miR-16-5p as the most potential biomarkers for monitoring resistance to chemotherapy. Finally, long non-coding RNAs that have been introduced in recent studies as novel biomarkers during the response to chemotherapy were mentioned.

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CD59 receptor targeted delivery of miRNA-1284 and Cisplatin-loaded liposomes for effective therapeutic efficacy against cervical cancers

10.21203/rs.2.22723/v1 ◽

2020 ◽

Author(s):

Li Wang ◽

Ting-Ting Liang

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Targeted Delivery ◽

Blood Circulation ◽

Anticancer Effect ◽

Killing Effect ◽

Cervical Cancers ◽

Cervical Cancer Cells ◽

Dependent Cell ◽

Cell Killing Effect

Abstract Co-delivery of two different therapeutics (miRNA-1284 and cisplatin (CDDP)) into the cancer cells in a single nanocarrier provides new dimension to the cancer treatment. In this study, we have designed the CD59sp-conjugated miRNA-1284/cisplatin(CDDP)-loaded liposomes for the enhanced therapeutic effect against cervical cancers. Compared with miRNA-1284/CDDP-loaded liposomes (LP-miCDDP), CD59 antibody-conjugated LP-miCDDP (CD/LP-miCDDP) showed a significantly higher cytotoxicity in HeLa cells. Notably, MiR-1284 showed a typical concentration-dependent cell killing effect in the cervical cancer cells owing to the downregulation of HMGB1. Flow cytometer analysis showed that CD/LP-miCDDP resulted in maximum apoptosis effect (~60%) compared to CDDP (~20%) or miR-1284 (~12%) treated cells indicating the superior anticancer effect in the cancer cells. Importantly, CD/LP-miCDDP significantly prolonged the blood circulation of encapsulated drug in rats with significantly higher AUC (o-t) , t 1/2 and lower CL compared to that of free CDDP. Overall, results demonstrated that targeted and synergistic co-delivery of therapeutic components could be promising in cervical cancer therapy.

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Mutation Analysis of Radioresistant Early-Stage Cervical Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms23010051 ◽

2021 ◽

Vol 23 (1) ◽

pp. 51

Author(s):

Tae Oike ◽

Yoshihito Sekiguchi ◽

Yuya Yoshimoto ◽

Takahiro Oike ◽

Ken Ando ◽

...

Keyword(s):

Cervical Cancer ◽

Local Recurrence ◽

Cancer Cells ◽

Early Stage ◽

Gene Set Enrichment Analysis ◽

Definitive Treatment ◽

Mesenchymal Transition ◽

X Ray ◽

Cervical Cancers ◽

Early Stage Cervical Cancer

Radiotherapy is a definitive treatment for early-stage cervical cancer; however, a subset of this disease recurs locally, necessitating establishment of predictive biomarkers and treatment strategies. To address this issue, we performed gene panel-based sequencing of 18 stage IB cervical cancers treated with definitive radiotherapy, including two cases of local recurrence, followed by in vitro and in silico analyses. Simultaneous mutations in KRAS and SMAD4 (KRASmt/SMAD4mt) were detected only in a local recurrence case, indicating potential association of this mutation signature with radioresistance. In isogenic cell-based experiments, a combination of activating KRAS mutation and SMAD4 deficiency led to X-ray resistance, whereas either of these factors alone did not. Analysis of genomic data from 55,308 cancers showed a significant trend toward co-occurrence of mutations in KRAS and SMAD4. Gene Set Enrichment Analysis of the Cancer Cell Line Encyclopedia dataset suggested upregulation of the pathways involved in epithelial mesenchymal transition and inflammatory responses in KRASmt/SMAD4mt cancer cells. Notably, irradiation with therapeutic carbon ions led to robust killing of X-ray-resistant KRASmt/SMAD4mt cancer cells. These data indicate that the KRASmt/SMAD4mt signature is a potential predictor of radioresistance, and that carbon ion radiotherapy is a potential option to treat early-stage cervical cancers with the KRASmt/SMAD4mt signature.

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