دورية أكاديمية

Tirbanibulin decreases cell proliferation and downregulates protein expression of oncogenic pathways in human papillomavirus containing HeLa cells.

التفاصيل البيبلوغرافية
العنوان: Tirbanibulin decreases cell proliferation and downregulates protein expression of oncogenic pathways in human papillomavirus containing HeLa cells.
المؤلفون: Moore S; Department of Dermatology, The University of Texas McGovern Medical School, Houston, TX, USA.; Department of Biosciences, Rice University, Houston, TX, USA., Kulkarni V; Department of Dermatology, The University of Texas McGovern Medical School, Houston, TX, USA., Moore A; Department of Dermatology, Baylor University Medical Center Part of Baylor Scott and White, Dallas, TX, USA., Landes JR; Department of Dermatology, The University of Texas McGovern Medical School, Houston, TX, USA., Simonette R; Department of Dermatology, The University of Texas McGovern Medical School, Houston, TX, USA., He Q; Department of Dermatology, The University of Texas McGovern Medical School, Houston, TX, USA., Rady PL; Department of Dermatology, The University of Texas McGovern Medical School, Houston, TX, USA., Tyring SK; Department of Dermatology, The University of Texas McGovern Medical School, Houston, TX, USA. styring@ccstexas.com.
المصدر: Archives of dermatological research [Arch Dermatol Res] 2024 Jul 05; Vol. 316 (7), pp. 455. Date of Electronic Publication: 2024 Jul 05.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Verlag Country of Publication: Germany NLM ID: 8000462 Publication Model: Electronic Cited Medium: Internet ISSN: 1432-069X (Electronic) Linking ISSN: 03403696 NLM ISO Abbreviation: Arch Dermatol Res Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Berlin : Springer Verlag
مواضيع طبية MeSH: Cell Proliferation*/drug effects , Oncogene Proteins, Viral*/metabolism , Down-Regulation*/drug effects , Human papillomavirus 18*, Humans ; HeLa Cells ; Papillomavirus Infections/virology ; Papillomavirus Infections/drug therapy ; Papillomavirus E7 Proteins/metabolism ; Apoptosis/drug effects ; Repressor Proteins/metabolism ; Repressor Proteins/genetics ; Signal Transduction/drug effects ; Uterine Cervical Neoplasms/virology ; Uterine Cervical Neoplasms/drug therapy ; Uterine Cervical Neoplasms/pathology ; Uterine Cervical Neoplasms/metabolism ; src-Family Kinases/metabolism ; src-Family Kinases/antagonists & inhibitors ; Female ; Human Papillomavirus Viruses ; DNA-Binding Proteins
مستخلص: Tirbanibulin 1% ointment is a synthetic antiproliferative agent approved in 2021 by the European Union for treating actinic keratoses (AK). Topical tirbanibulin has clinically resolved HPV-57 ( +) squamous cell carcinoma (SCC), HPV-16 ( +) vulvar high-grade squamous intraepithelial lesion, epidermodysplasia verruciformis, and condyloma. We examined how tirbanibulin might affect HPV oncoprotein expression and affect other cellular pathways involved in cell proliferation and transformation. We treated the HeLa cell line, containing integrated HPV-18, with increasing doses of tirbanibulin to determine the effects on cell proliferation. Immunoblotting was performed with antibodies against the Src canonical pathway, HPV 18 E6 and E7 transcription regulation, apoptosis, and invasion and metastasis pathways. Cell proliferation assays with tirbanibulin determined the half-maximal inhibitory concentration (IC 50 ) of HeLa cells to be 31.49 nmol/L. Increasing concentrations of tirbanibulin downregulates the protein expression of Src (p < 0.001), phospho-Src (p < 0.001), Ras (p < 0.01), c-Raf (p < 0.001), ERK1 (p < 0.001), phospho-ERK1 (p < 0.001), phospho-ERK2 (p < 0.01), phospho-Mnk1 (p < 0.001), eIF4E (p < 0.01), phospho-eIF4E (p < 0.001), E6 (p < 0.01), E7 (p < 0.01), Rb (p < 0.01), phospho-Rb (p < 0.001), MDM2 (p < 0.01), E2F1 (p < 0.001), phospho-FAK (p < 0.001), phospho-p130 Cas (p < 0.001), Mcl-1 (p < 0.01), and Bcl-2 (p < 0.001), but upregulates cPARP (p < 0.001), and cPARP/fPARP (p < 0.001). These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins via the Src- MEK- pathway. Tirbanibulin significantly downregulates oncogenic proteins related to cell cycle regulation and cell proliferation while upregulating apoptosis pathways.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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فهرسة مساهمة: Keywords: Human papillomavirus; Novel treatment; Skin disease; Tirbanibulin; Topical treatment
Local Abstract: [plain-language-summary] Tirbanibulin is Promising Novel Therapy for Human Papillomavirus (HPV)-associated Diseases.Tirbanibulin 1% ointment is an approved synthetic topical ointment for treating actinic keratoses (AK), a precancer of skin cancer. Topical tirbanibulin has previously been reported to clinically resolve human papillomavirus (HPV)-( +) diseases.In this study, we examine how tirbanibulin may affect the HPV and pathways associated with cancer.We treated the HeLa cell line to determine the effects on HPV cell proliferation. Increasing the concentration of tirbanibulin statistically significantly affected numerous cellular pathways often associated with cancer.These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins and thereby kill cancer cells.
المشرفين على المادة: 0 (Oncogene Proteins, Viral)
0 (E6 protein, Human papillomavirus type 18)
0 (E7 protein, Human papillomavirus type 18)
0 (Papillomavirus E7 Proteins)
0 (Repressor Proteins)
EC 2.7.10.2 (src-Family Kinases)
0 (DNA-Binding Proteins)
تواريخ الأحداث: Date Created: 20240705 Date Completed: 20240705 Latest Revision: 20240705
رمز التحديث: 20240705
DOI: 10.1007/s00403-024-03205-8
PMID: 38967656
قاعدة البيانات: MEDLINE
الوصف
تدمد:1432-069X
DOI:10.1007/s00403-024-03205-8