Involvement of p53-dependent apoptosis signal in antitumor effect of Colchicine on human papilloma virus (HPV)-positive human cervical cancer cells

Abstract Colchicine, a plant-derived alkaloid with relatively low toxicity on normal human epidermal keratinocytes (HEKn), has selective inhibitory effect on the growth of CaSki (HPV16-positive) and HeLa (HPV18-positive) human cervical cancer cell lines via the induction of apoptosis. Colchicine (2.5, 5.0 and 10.0 ng/ml) significantly reduced the expression of human papilloma virus (HPV) 16 E6/E7 mRNA and protein in CaSki and HeLa cells. Moreover, reduced expression of E6 and E7 induced by Colchicine resulted in the up-regulation of tumor suppressor proteins, p53 and Rb, as well as down-regulation of phospho Rb (pRb) protein. In addition, Bax, cytosolic cytochrome c and cleaved caspase-3 protein were increased while Bcl-2 protein was decreased significantly by 48 h of Colchicine treatment. These results implied that Colchicine could be explored as a potent candidate agent for the treatment and prevention of HPV-associated cervical cancer without deleterious effects.

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A Comprehensive Review on Crosstalk of Human Papilloma Virus oncoproteins and developmental/self-renewal pathways during the pathogenesis of uterine cervical cancer

Current Molecular Medicine ◽

10.2174/1566524020666200925160015 ◽

2020 ◽

Vol 20 ◽

Author(s):

Afza Ahmad ◽

Irfan Ahmad Ansari

Keyword(s):

Cervical Cancer ◽

Human Papilloma Virus ◽

Epithelial Mesenchymal Transition ◽

Wnt Signaling Pathway ◽

Hpv Infection ◽

Uterine Cervical Cancer ◽

Self Renewal ◽

Papilloma Virus ◽

Mesenchymal Transition ◽

E6 And E7

: Cervical cancer, a cancer arising from the uterine cervix has been regarded as the fourth most frequent gynecological malignancy among females worldwide. Epidemiological reports have shown that uterine cervical cancer is a global health issue among womens of specially developing countries and consequently creates an economic and medical burden in the society. The main causative agent of cervical carcinoma is high risk human papilloma virus (HPV 16 and HPV 18). Molecular studies have revealed the expression two viral genes E6 and E7 after HPV infection in the epithelial cells of cervix. These gene products are known to inactivate the major tumor suppressors, p53 and retinoblastoma protein (pRB), respectively. Moreover, the role of self-renewal pathways such as Hedgehog, Notch and Wnt has also been linked with drug resistance in cancer cells and epithelial mesenchymal transition during metastasis in pathogenesis of cervical cancer. Although, the mechanism of interaction of HPV E6 and E7 with each and every component of above described developmental pathways is not elucidated yet, but preliminary reports of their crosstalk have begun to emerge. Understanding the interplay between these oncoproteins and developmental/self-renewal pathways is highly important in terms of designing new and targeted therapeutic approach against cervical cancer. Hence, this review cynosure the carcinogenesis of HPV with the brief description of its virology and also establishes the crosstalk between oncoproteins E6 & E7 and Hedgehog, Notch and Wnt signaling pathway.

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E6 and E7 oncogene expression by human papilloma virus (HPV) and the aggressive behavior of recurrent laryngeal papillomatosis (RLP)

Pediatric and Developmental Pathology ◽

10.2350/06-09-0160 ◽

2006 ◽

Vol preprint (2007) ◽

pp. 1

Author(s):

Bahig Shehata ◽

Kristen Otto ◽

Steven Sobol ◽

Christina Stockwell ◽

Cora Foulks ◽

...

Keyword(s):

Human Papilloma Virus ◽

Aggressive Behavior ◽

Laryngeal Papillomatosis ◽

Papilloma Virus ◽

Oncogene Expression ◽

E6 And E7 ◽

E7 Oncogene

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More than 97% of Human Papilloma Virus Type 16 (HPV-16) was Found with Chrysotile Asbestos & Relatively Smooth Round Tumor Outline, and Less than 3% was found with HPV-18 and Tremolite Asbestos & Irregular Sawtooth-like Zigzag Outline in Breast Cancer Tissues in Over 500 Mammograms of Female Patients: Their Implications in Diagnosis, Treatment, and Prevention of Breast Cancer

Acupuncture & Electro-Therapeutics Research ◽

10.3727/036012913x13831832269324 ◽

2013 ◽

Vol 38 (3) ◽

pp. 211-230 ◽

Cited By ~ 2

Author(s):

Yoshiaki Omura ◽

Marilyn K Jones ◽

Abdallah Nihrane ◽

Harsha Duvvi ◽

Yasuhiro Shimotsuura ◽

...

Keyword(s):

Breast Cancer ◽

Human Papilloma Virus ◽

Virus Type ◽

Human Papilloma Virus Type ◽

Chrysotile Asbestos ◽

Papilloma Virus ◽

Treatment And Prevention ◽

Cancer Tissues ◽

Prevention Of Breast Cancer ◽

Hpv 18

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Human papilloma virus status in cervical cancer predictive and prognostic significance for chemo radiation treatment

Asian Pacific Journal of Health Sciences ◽

10.21276/apjhs.2016.3.4.30 ◽

2016 ◽

Vol 3 (4) ◽

pp. 189-198

Author(s):

Madisetty Adi Lakshmi ◽

◽

M Vishnu Priya ◽

Chinta Sanjeeva kumari ◽

◽

...

Keyword(s):

Cervical Cancer ◽

Human Papilloma Virus ◽

Radiation Treatment ◽

Prognostic Significance ◽

Papilloma Virus ◽

Human Papilloma Virus Status

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A Synopsis on the Role of Human Papilloma Virus Infection in Cervical Cancer

Current Drug Metabolism ◽

10.2174/1389200219666180302160317 ◽

2018 ◽

Vol 19 (9) ◽

pp. 798-805 ◽

Cited By ~ 1

Author(s):

Mohd Saeed ◽

Fawaz D. Alshammari ◽

Md. Jahoor Alam ◽

Khan Mohd Sarim ◽

Khurshid Ahmad ◽

...

Keyword(s):

Cervical Cancer ◽

Virus Infection ◽

Human Papilloma Virus ◽

Human Papilloma Virus Infection ◽

Papilloma Virus

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309PD Features of cervical cancer in HIV-infected and uninfected women in association with human papilloma virus

Annals of Oncology ◽

10.1093/annonc/mdw585.013 ◽

2016 ◽

Vol 27 (suppl_9) ◽

Author(s):

M.N. Tashmetov

Keyword(s):

Cervical Cancer ◽

Human Papilloma Virus ◽

Papilloma Virus

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The Inhibitory Effect of a Novel Polypeptide Fraction fromArca subcrenataon Cancer-Related Inflammation in Human Cervical Cancer HeLa Cells

The Scientific World JOURNAL ◽

10.1155/2014/768938 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Yu Wu ◽

Xianjing Hu ◽

Liyan Song ◽

Jianhua Zhu ◽

Rongmin Yu

Keyword(s):

Cervical Cancer ◽

Hela Cells ◽

Molecular Mechanisms ◽

Tumor Development ◽

Basic Research ◽

Inhibitory Effect ◽

Fishery Resource ◽

Proinflammatory Mediators ◽

Raw264.7 Macrophage ◽

Human Cervical Cancer

Inflammation is known to be closely associated with the development of cancer. The study was launched in human cervical cancer HeLa cells to investigate the antitumor and anti-inflammatory effects of P2, a marine polypeptide fraction from an important fishery resourceArca subcrenata. The basic research showed that P2 could suppress the production of nitric oxide in LPS-induced RAW264.7 macrophage cells as well as the secretion of inflammatory cytokines IL-6 and TNF-αin human cervical cancer HeLa cells. For the molecular mechanisms, P2 was shown to downregulate the gene expression of proinflammatory cytokines IL-6 and IL-8 and to inhibit the COX-2 and iNOS-related pathways in HeLa cells. In consequence, P2 might inhibit tumor development by blocking the interaction between tumor microenvironment and proinflammatory mediators. All findings indicate that P2 possesses the potential to be developed as a novel agent for cancer therapy.

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