Tirbanibulin decreases cell proliferation and downregulates protein expression of oncogenic pathways in human papillomavirus containing HeLa cells.
Humans
HeLa Cells
Cell Proliferation
/ drug effects
Oncogene Proteins, Viral
/ metabolism
Down-Regulation
/ drug effects
Human papillomavirus 18
Papillomavirus Infections
/ virology
Papillomavirus E7 Proteins
/ metabolism
Apoptosis
/ drug effects
Repressor Proteins
/ metabolism
Signal Transduction
/ drug effects
Uterine Cervical Neoplasms
/ virology
src-Family Kinases
/ metabolism
Female
Human Papillomavirus Viruses
DNA-Binding Proteins
Human papillomavirus
Novel treatment
Skin disease
Tirbanibulin
Topical treatment
Journal
Archives of dermatological research
ISSN: 1432-069X
Titre abrégé: Arch Dermatol Res
Pays: Germany
ID NLM: 8000462
Informations de publication
Date de publication:
05 Jul 2024
05 Jul 2024
Historique:
received:
11
05
2024
accepted:
23
06
2024
revised:
18
06
2024
medline:
5
7
2024
pubmed:
5
7
2024
entrez:
5
7
2024
Statut:
epublish
Résumé
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 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.
Autres résumés
Type: plain-language-summary
(eng)
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.
Identifiants
pubmed: 38967656
doi: 10.1007/s00403-024-03205-8
pii: 10.1007/s00403-024-03205-8
doi:
Substances chimiques
Oncogene Proteins, Viral
0
E6 protein, Human papillomavirus type 18
0
E7 protein, Human papillomavirus type 18
0
Papillomavirus E7 Proteins
0
Repressor Proteins
0
src-Family Kinases
EC 2.7.10.2
DNA-Binding Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
455Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Blauvelt A, Kempers S, Lain E et al (2021) Phase 3 trials of tirbanibulin ointment for actinic keratosis. N Engl J Med 384(6):512–520. https://doi.org/10.1056/NEJMoa2024040
doi: 10.1056/NEJMoa2024040
pubmed: 33567191
Moore A, Hurley K, Moore S, Moore L (2023) Topical tirbanibulin resolves recalcitrant condyloma acuminata: retrospective case series. JAAD Case Rep. https://doi.org/10.1016/j.jdcr.2023.04.011
doi: 10.1016/j.jdcr.2023.04.011
pubmed: 37842153
pmcid: 10477357
Moore AY, Moore SA, He Q, Rady P, Tyring SK (2022) Tirbanibulin 1% ointment eradicates HPV-16 (+) vulvar high-grade squamous intraepithelial lesion. J Eur Acad Dermatol Venereol 36(10):e784–e785. https://doi.org/10.1111/jdv.18265
doi: 10.1111/jdv.18265
pubmed: 35608184
Moore AY, Moore SA, He Q, Rady P, Tyring SK (2022) HPV-57 (+) in periungual squamous cell carcinoma eradicated by topical tirbanibulin. JAAD Case Rep. Published online February 10. https://doi.org/10.1016/j.jdcr.2022.01.021
Bunda S, Heir P, Srikumar T et al (2014) Src promotes GTPase activity of Ras via tyrosine 32 phosphorylation. Proc Natl Acad Sci U S A 111(36):E3785-3794. https://doi.org/10.1073/pnas.1406559111
doi: 10.1073/pnas.1406559111
pubmed: 25157176
pmcid: 4246987
Stokoe D, McCormick F (1997) Activation of c-Raf-1 by Ras and Src through different mechanisms: activation in vivo and in vitro. EMBO J 16(9):2384–2396. https://doi.org/10.1093/emboj/16.9.2384
doi: 10.1093/emboj/16.9.2384
pubmed: 9171352
pmcid: 1169839
Schlesinger T, Stockfleth E, Grada A, Berman B (2022) Tirbanibulin for actinic keratosis: insights into the mechanism of action. Clin Cosmet Investig Dermatol 15:2495–2506. https://doi.org/10.2147/CCID.S374122
doi: 10.2147/CCID.S374122
pubmed: 36415541
pmcid: 9675993
Pelaz SG, Tabernero A (2022) Src: coordinating metabolism in cancer. Oncogene 41(45):4917–4928. https://doi.org/10.1038/s41388-022-02487-4
doi: 10.1038/s41388-022-02487-4
pubmed: 36217026
pmcid: 9630107
Wang J, Aldabagh B, Yu J, Arron ST (2014) Role of human papillomavirus in cutaneous squamous cell carcinoma: a Meta-analysis. J Am Acad Dermatol 70(4):621–629. https://doi.org/10.1016/j.jaad.2014.01.857
doi: 10.1016/j.jaad.2014.01.857
pubmed: 24629358
pmcid: 3959664
Kim S, Min A, Lee KH et al (2017) Antitumor effect of KX-01 through inhibiting Src family kinases and mitosis. Cancer Res Treat 49(3):643–655. https://doi.org/10.4143/crt.2016.168
doi: 10.4143/crt.2016.168
pubmed: 27737538
Gilaberte Y, Fernández-Figueras MT (2021) Tirbanibulin: review of its novel mechanism of action and how it fits into the treatment of actinic keratosis. Actas Dermo-Sifiliográficas Engl Ed. https://doi.org/10.1016/j.adengl.2021.11.010
doi: 10.1016/j.adengl.2021.11.010
Szalmás A, Gyöngyösi E, Ferenczi A et al (2013) Activation of Src, Fyn and Yes non-receptor tyrosine kinases in keratinocytes expressing human papillomavirus (HPV) type 16 E7 oncoprotein. Virol J 10(1):79. https://doi.org/10.1186/1743-422X-10-79
doi: 10.1186/1743-422X-10-79
pubmed: 23497302
pmcid: 3608944
Kong L, Deng Z, Zhao Y, Wang Y, Sarkar FH, Zhang Y (2011) Down-regulation of phospho-non-receptor Src tyrosine kinases contributes to growth inhibition of cervical cancer cells. Med Oncol Northwood Lond Engl 28(4):1495–1506. https://doi.org/10.1007/s12032-010-9583-3
doi: 10.1007/s12032-010-9583-3
Pal A, Kundu R (2020) Human papillomavirus E6 and E7: The cervical cancer hallmarks and targets for therapy. Front Microbiol 10:3116. https://doi.org/10.3389/fmicb.2019.03116
doi: 10.3389/fmicb.2019.03116
pubmed: 32038557
pmcid: 6985034
Morales-Garcia V, Contreras-Paredes A, Martinez-Abundis E et al (2020) The high-risk HPV E6 proteins modify the activity of the eIF4E protein via the MEK/ERK and AKT/PKB pathways. FEBS Open Bio 10(12):2541–2552. https://doi.org/10.1002/2211-5463.12987
doi: 10.1002/2211-5463.12987
pubmed: 32981220
pmcid: 7714072
Gao SY, Li EM, Cui L et al (2009) Sp1 and AP-1 regulate expression of the human gene VIL2 in esophageal carcinoma cells. J Biol Chem 284(12):7995–8004. https://doi.org/10.1074/jbc.M809734200
doi: 10.1074/jbc.M809734200
pubmed: 19164283
pmcid: 2658093
Siddiqui N, Sonenberg N (2015) Signalling to eIF4E in cancer. Biochem Soc Trans 43(5):763–772. https://doi.org/10.1042/BST20150126
doi: 10.1042/BST20150126
pubmed: 26517881
pmcid: 4613458
Idres YM, Lai AJ, McMillan NAJ, Idris A (2023) Hyperactivation of p53 using CRISPRa kills human papillomavirus-driven cervical cancer cells. Virus Genes 59(2):312–316. https://doi.org/10.1007/s11262-022-01960-2
doi: 10.1007/s11262-022-01960-2
pubmed: 36474086
Shu KX, Li B, Wu LX (2007) The p53 network: p53 and its downstream genes. Colloids Surf B Biointerfaces 55(1):10–18. https://doi.org/10.1016/j.colsurfb.2006.11.003
doi: 10.1016/j.colsurfb.2006.11.003
pubmed: 17188467
Drosten M, Sum EYM, Lechuga CG et al (2014) Loss of p53 induces cell proliferation via Ras-independent activation of the Raf/Mek/Erk signaling pathway. Proc Natl Acad Sci USA 111(42):15155–15160. https://doi.org/10.1073/pnas.1417549111
doi: 10.1073/pnas.1417549111
pubmed: 25288756
pmcid: 4210339
Montero J, Dutta C, van Bodegom D, Weinstock D, Letai A (2013) p53 regulates a non-apoptotic death induced by ROS. Cell Death Differ 20(11):1465–1474. https://doi.org/10.1038/cdd.2013.52
doi: 10.1038/cdd.2013.52
pubmed: 23703322
pmcid: 3792438
Chaitanya GV, Alexander JS, Babu PP (2010) PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration. Cell Commun Signal 8(1):31. https://doi.org/10.1186/1478-811X-8-31
Kaufmann SH, Desnoyers S, Ottaviano Y, Davidson NE, Poirier GG (1993) Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. Cancer Res 53(17):3976–3985
pubmed: 8358726
Antonucci LA, Egger JV, Krucher NA (2014) Phosphorylation of the Retinoblastoma protein (Rb) on serine-807 is required for association with Bax. Cell Cycle 13(22):3611–3617. https://doi.org/10.4161/15384101.2014.964093
doi: 10.4161/15384101.2014.964093
pubmed: 25483096
pmcid: 4614104
Yoon H, Dehart JP, Murphy JM, Lim STS (2015) Understanding the roles of FAK in cancer. J Histochem Cytochem 63(2):114–128. https://doi.org/10.1369/0022155414561498
doi: 10.1369/0022155414561498
pubmed: 25380750
Luo J, Zou H, Guo Y et al (2022) SRC kinase-mediated signaling pathways and targeted therapies in breast cancer. Breast Cancer Res 24(1):99. https://doi.org/10.1186/s13058-022-01596-y
doi: 10.1186/s13058-022-01596-y
pubmed: 36581908
pmcid: 9798727
Wu Y, Li N, Ye C et al (2021) Focal adhesion kinase inhibitors, a heavy punch to cancer. Discov Oncol 12:52. https://doi.org/10.1007/s12672-021-00449-y
doi: 10.1007/s12672-021-00449-y
pubmed: 35201485
pmcid: 8777493
Li J, Zhang X, Hou Z et al (2022) P130cas-FAK interaction is essential for YAP-mediated radioresistance of non-small cell lung cancer. Cell Death Dis 13(9):1–15. https://doi.org/10.1038/s41419-022-05224-7
doi: 10.1038/s41419-022-05224-7
Kumbrink J, Kirsch KH, Kumbrink J, Kirsch KH (2011) Targeting cas family proteins as a novel treatment for breast cancer. In: Breast cancer - current and alternative therapeutic modalities. IntechOpen https://doi.org/10.5772/21227
Jackson RJ, Hellen CUT, Pestova TV (2010) The mechanism of eukaryotic translation initiation and principles of its regulation. Nat Rev Mol Cell Biol 11(2):113–127. https://doi.org/10.1038/nrm2838
doi: 10.1038/nrm2838
pubmed: 20094052
pmcid: 4461372
Zhu Y, Wang C, Li M, Yang X (2021) Targeting of MNK/eIF4E overcomes chemoresistance in cervical cancer. J Pharm Pharmacol 73(10):1418–1426. https://doi.org/10.1093/jpp/rgab094
doi: 10.1093/jpp/rgab094
pubmed: 34254647
Zhang W, Su X, Li S, Wang Y, Wang Q, Zeng H (2019) Inhibiting MNK selectively targets cervical cancer via suppressing eIF4E-mediated β-catenin activation. Am J Med Sci 358(3):227–234. https://doi.org/10.1016/j.amjms.2019.05.013
doi: 10.1016/j.amjms.2019.05.013
pubmed: 31327462
Sears RC, Nevins JR (2002) Signaling networks that link cell proliferation and cell fate*. J Biol Chem 277(14):11617–11620. https://doi.org/10.1074/jbc.R100063200
doi: 10.1074/jbc.R100063200
pubmed: 11805123
Ahmadi SE, Rahimi S, Zarandi B, Chegeni R, Safa M (2021) MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies. J Hematol OncolJ Hematol Oncol 14(1):121. https://doi.org/10.1186/s13045-021-01111-4
doi: 10.1186/s13045-021-01111-4
García-Gutiérrez L, Delgado MD, León J (2019) MYC oncogene contributions to release of cell cycle brakes. Genes 10(3):244. https://doi.org/10.3390/genes10030244
doi: 10.3390/genes10030244
pubmed: 30909496
pmcid: 6470592
De Zio D, Cianfanelli V, Cecconi F (2013) New Insights into the link between DNA damage and apoptosis. Antioxid Redox Signal 19(6):559–571. https://doi.org/10.1089/ars.2012.4938
doi: 10.1089/ars.2012.4938
pubmed: 23025416
pmcid: 3717195
Caner A, Asik E, Ozpolat B (2021) SRC Signaling in cancer and tumor microenvironment. In: Birbrair A, ed. Tumor microenvironment: signaling pathways – Part B. Advances in experimental medicine and biology. Springer International Publishing; https://doi.org/10.1007/978-3-030-47189-7_4
Morgan EL, Scarth JA, Patterson MR et al (2021) E6-mediated activation of JNK drives EGFR signalling to promote proliferation and viral oncoprotein expression in cervical cancer. Cell Death Differ 28(5):1669–1687. https://doi.org/10.1038/s41418-020-00693-9
doi: 10.1038/s41418-020-00693-9
pubmed: 33303976
Wheeler DL, Iida M, Dunn EF (2009) The role of Src in solid tumors. Oncologist 14(7):667–678. https://doi.org/10.1634/theoncologist.2009-0009
doi: 10.1634/theoncologist.2009-0009
pubmed: 19581523
Moumen A, Patané S, Porras A, Dono R, Maina F (2007) Met acts on Mdm2 via mTOR to signal cell survival during development. Development 134(7):1443–1451. https://doi.org/10.1242/dev.02820
doi: 10.1242/dev.02820
pubmed: 17329361
Haura EB (2006) SRC and STAT pathways. J Thorac Oncol 1(5):403–405. https://doi.org/10.1016/S1556-0864(15)31601-4
doi: 10.1016/S1556-0864(15)31601-4
pubmed: 17409890
Kung CP, Weber JD (2022) It’s getting complicated—a fresh look at p53-MDM2-ARF triangle in tumorigenesis and cancer therapy. Front Cell Dev Biol. Accessed October 9, 2023. https://www.frontiersin.org/articles/ https://doi.org/10.3389/fcell.2022.818744