Modulation of apoptosis by early human papillomavirus proteins in cervical cancer

Lagunas‐Martínez, Alfredo; Madrid‐Marina, Vicente; Gariglio, Patricio

doi:10.1016/j.bbcan.2009.03.005

Cited by 38 publications

(38 citation statements)

References 146 publications

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“…S6A). Cleavage of procaspases and PARP is the molecular hallmark of apoptotic cell death (20). Treatment of ACHN cells with either compound 4 or compound 8 caused the cleavage of caspase-8 and PARP, whereas other compounds did not (Fig.…”

Section: Selected Chemicals Induce Dynap-dependent Apoptosis Of Humanmentioning

confidence: 99%

A Novel Human Dynactin-Associated Protein, dynAP, Promotes Activation of Akt, and Ergosterol-Related Compounds Induce dynAP-Dependent Apoptosis of Human Cancer Cells

Kunoh

Noda

Koseki

et al. 2010

Molecular Cancer Therapeutics

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There are several human genes that may encode proteins whose functions remain unknown. To find clues to their functions, we used the mutant yeast defective in Mad2, a component of the spindle checkpoint complex. Phenotypes that were provoked by the expression of a human C18orf26 protein in the mutant yeast encouraged further characterization of this protein in human cells. This protein was designated dynAP (dynactin-associated protein) because of its interaction with dynactin subunits that comprised a microtubule-based motor protein complex. The dynAP is a transmembrane protein localizing to Golgi apparatus and plasma membrane in a microtubule-dependent manner. This protein was expressed in half of human cancer cell lines but barely in normal human fibroblasts tested. The SV40-transformed fibroblasts expressed dynAP. Importantly, the expression of dynAP activated Akt (also known as protein kinase B) by promoting Ser 473 phosphorylation required for the full activation, whereas knockdown of dynAP abolished this activation. The ergosterol-related compounds identified by the yeast cell-based high-throughput screen abrogated activation of Akt and induced apoptosis in a dynAP-dependent manner. We propose a possible advantage of dynAP expression in cancer cells; the survival of cancer cells that express dynAP is supported by dynAP-induced activation of Akt, sustaining high rates of proliferation. The inactivation of dynAP by the selected compounds nullifies this advantage, and thereby, the apoptotic machinery is allowed to operate. Taken together, dynAP can be a new target for cancer therapy, and the selected chemicals are useful for developing a new class of anticancer drugs.

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Section: Selected Chemicals Induce Dynap-dependent Apoptosis Of Humanmentioning

confidence: 99%

A Novel Human Dynactin-Associated Protein, dynAP, Promotes Activation of Akt, and Ergosterol-Related Compounds Induce dynAP-Dependent Apoptosis of Human Cancer Cells

Kunoh

Noda

Koseki

et al. 2010

Molecular Cancer Therapeutics

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“…Western blot analysis was performed on HeLa cell (cervical cancer cell invected with human papillomavirus-18) express protein E6 and E7 that disrupt p53 and pRb suppressor protein [12][13][14]. The experiment also was conducted on MCF-7, a breast cancer cell line that expresses normal p53 protein [15], but does not express caspase-3 [16] compared to the other breast cancer cell lines type T47D that had mutation on p53 gen [17].…”

Section: Resultsmentioning

confidence: 99%

“…4). It might be caused by protein E6 that was expressed by HeLa cells that degraded p53 as a transcription factor of PUMA and BAX [13,14]. Apoptosis induction on HeLa cells might involve and extrinsic pathway.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis Induction Effect of Curcumin and Its Analogs Pentagamavunon-0 and Pentagamavunon-1 on Cancer Cell Lines

Da'i

Suhendi

Meiyanto

et al. 2017

Asian J Pharm Clin Res

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Objectives: This experiment aims to investigate the apoptosis effect of curcumin and its analogs pentagamavunon-0 (PGV-0) and PGV-1 on normal and other cancer cell lines.Methods: Growth inhibition effect was investigated using the MTT method. Double staining used acridine orange, 2-(4-aminodiphenyl)-6-indolcarbamidine dihydrochloride and ethidium bromide was performed to determine morphological changes of cells. Detection of PARP, caspase-3, PUMA and BAX using a western blot method was conducted to elucidate the apoptosis effect of the compounds.Results: PGV-1 (2.5 μM) and PGV-0 (5.0 μM) could inhibit T47D-cell growth on 72 h observation, but not for curcumin. DNA staining showed PGV-1 has the strongest apoptosis induction effect on T47D-cells compared to PGV-0 and curcumin as well. Western blot analysis resulted in cleavage PARP (83 kD) on HeLa, T47D, and MCF-7 cells treated with PGV-1 (2.5 µM), PGV-0 (5.0 µM). Curcumin (10.0 µM) just induced apoptosis on T47D-cell and MCF-7 cell, but not HeLa cell. Cleavage PARP resulted by apoptosis process in the cell. PGV-1 (2.5 µM) had a stronger apoptosis effect compared to PGV-0 (5.0 µM) and curcumin (10.0 µM) based on cleaved PARP result qualitatively. On the normal cell (NH3T3), cells that were treated with the compounds resulted in a negative cleavage PARP. This result indicated that the compounds were part of a selectively induced cancer cell line apoptosis process. Conclusion:Curcumin, PGV-0 and PGV-1 could inhibit cell growth by induce apoptosis on cancer cells but not on normal cells, which PGV-1 has strongest apoptosis induction effect on cancer cell lines.

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“…Несмотря на то что роль HPV в развитии дисплазии и РШМ установлена точно, возникновение этого патологи-ческого процесса невозможно без дополнительных изме-нений генома клеток, происходящего в результате инте-грации генома HPV в геном хозяина [15]. Процесс инте-грации генома HPV связан с переходом дисплазии низкой степени в дисплазию высокой степени.…”

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The etiology and pathogenesis of cervical intraepithelial neoplasias: Review of foreign literature

Levakov¹,

Шешукова²,

Дабагян³

2016

Ross. vestn. akush.-ginekol.

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Цервикальные интраэпителиальные неоплазии (CIN) представляют собой атипическую трансформацию пло-скоклеточного эпителия без инвазии в строму и являются факторами прогноза развития рака шейки матки (РШМ). Согласно классификации ВОЗ [1], выделяют низкую сте-пень эпителиального поражения шейки матки (CIN I -легкая дисплазия, плоская кондилома, койлоцитоз, кой-лоцитарная атипия) и высокую степень эпителиального поражения (CIN II-III, средняя и тяжелая степени дис-плазии, эпителиальная карцинома in situ).Ведущая роль в патогенезе патологических процессов в шейке матки принадлежит вирусу папилломы человека (HPV). Выделяемые реплицирующимся вирусом онко-белки Е6 и Е7 индуцируют активную пролиферацию диф-ференцированных клеток цервикального эпителия, что приводит к развитию CIN. На мышиных моделях канце-рогенеза шейки матки было показано, что Е7 приводит к развитию микроинвазивного рака, а Е6 не вызывал нео-плазию или рак [2]. Сочетание же экспрессии этих белков приводило к развитию высокоинвазивного РШМ. Выяв-лено, что экспрессия белка Е6 приводит к тому, что инфи-цированная клетка перестает реагировать на сигналы, уг-нетающие рост клеток, и не подвергается апоптозу. Ви-русный белок Е6 связывается с клеточным белком Е6-АР, e-mail: lusine.dabagyan@mail.ru На основании данных литературы обобщены результаты современных опубликованных исследований по проблеме церви-кальных интраэпителиальных неоплазий. Определена ведущая роль вирусов папилломы человека в этиологии и патогенезе патологических процессов в шейке матки, обращено внимание, что развитию цервикальной интраэпителиальной неопла-зии способствуют некоторые кофакторы невирусного происхождения: курение, применение пероральных контрацепти-вов, наличие родов в анамнезе, особенности генома иммунного статуса, а также инфицирование другими возбудителями заболеваний половых путей. Указаны различные риски и факторы развития дисплазии и рака шейки матки. Подчеркнуто, что риск развития инвазивного рака шейки матки значительно выше среди ВИЧ-инфицированных женщин.Авторы информируют об отсутствии конфликта интересов. Based on the data available in the literature, the authors generalize the results of current published studies on the problem of cervical intraepithelial neoplasias. They determine the leading role of human papillomavirus in the etiology and pathogenesis of pathological processes in the cervix uteri and call attention to the fact that the development of cervical intraepithelial neoplasia is favored by some non-viral cofactors: smoking, use of oral contraceptives, a birth history, genomic features of the immune status, and infection with other pathogens of genital tract diseases. Different risks and factors of cervical dysplasia and cancer are indicated. The risk of invasive cervical cancer is emphasized to be much higher among HIV-infected women. The authors declare no conflicts of interest.

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Modulation of apoptosis by early human papillomavirus proteins in cervical cancer

Cited by 38 publications

References 146 publications

A Novel Human Dynactin-Associated Protein, dynAP, Promotes Activation of Akt, and Ergosterol-Related Compounds Induce dynAP-Dependent Apoptosis of Human Cancer Cells

A Novel Human Dynactin-Associated Protein, dynAP, Promotes Activation of Akt, and Ergosterol-Related Compounds Induce dynAP-Dependent Apoptosis of Human Cancer Cells

Apoptosis Induction Effect of Curcumin and Its Analogs Pentagamavunon-0 and Pentagamavunon-1 on Cancer Cell Lines

The etiology and pathogenesis of cervical intraepithelial neoplasias: Review of foreign literature

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