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Cited by 16Photodynamic Therapy Research StudiesNonmelanoma Skin Cancer StudiesHead and Neck Cancer Studies

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Halofuginone enhances the anti-tumor effect of ALA-PDT by suppressing NRF2 signaling in cSCC

Lv, Ting, Huang, Jianhua, Wu, Minfeng, Wang, Hongwei, Zeng, Qingyu, Wang, Xiuli·2022·Photodiagnosis and Photodynamic Therapy
DOI 10.1016/j.pdpdt.2021.102572
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Abstract

Background 5-aminolevulinic acid-mediated PDT (ALA-PDT) has been used in a variety of skin diseases including cSCC (cutaneous squamous cell carcinoma). Halofuginone (HL) is a less-toxic febrifugine derivative and has inhibitory effects on a variety of cancer cells. For now, there are no published study focusing on the combination use of ALA-PDT with HL to improve clinical efficacy of cSCC. Objective In this study, we will examine the effectiveness of combined treatment of ALA-PDT and HL in cSCC as well as its underlying mechanism. Methods The human epidermoid carcinoma cell line SCL-1 was treated with ALA-PDT or/ and HL, and cell viability, cell migration, ROS production, apoptosis were evaluated by CCK-8, colony formation, scratch assay, DCFH-DA probe, flow cytometry, respectively. The protein expression of NRF2 signaling was examined by western blot. Results HL strengthened ALA-PDT's inhibition of SCL-1 cell viability, migration, as well as NRF2 related β-catenin, p-Erk1/2, p-Akt and p-S6K1 expression. Overexpression of NRF2 conferred resistance to co-treatment's effects on c-Myc, Cyclin D1, Bcl-2, as well as cell proliferation. HL also strengthened ALA-PDT's inhibition of tumor volume in cSCC mouse model and elevated ROS generation of ALA-PDT. Conclusion HL enhances the anti-tumor effect of ALA-PDT in vitro and in vivo. HL has the potential to enhance the anti-tumor effect of ALA-PDT in cSCC via inhibiting NRF2 signaling.

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References 35 · Cited by 16

Research works printed but not linked: 26

  1. Burden of Disease, 2019, Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2017: a systematic analysis for the global burden of disease study, JAMA Oncol., 5, 1749, 10.1001/jamaoncol.2019.2996 · DOI
  2. Schmults, 2013, Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study, JAMA Dermatol., 149, 541, 10.1001/jamadermatol.2013.2139 · DOI
  3. Brantsch, 2008, Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study, Lancet Oncol., 9, 713, 10.1016/S1470-2045(08)70178-5 · DOI
  4. Wang, 2008, Treatment of skin cancer and pre-cancer using topical ALA-PDT–a single hospital experience, Photodiagnosis Photodyn. Ther., 5, 127, 10.1016/j.pdpdt.2008.05.003 · DOI
  5. Skaria, 2014, European guidelines for topical PDT part 1 JEADV 2013; 27: 536-544, J. Eur. Acad. Dermatol. Venereol., 28, 673, 10.1111/jdv.12258 · DOI
  6. Cohen, 2016, Photodynamic therapy for non-melanoma skin cancers, Cancers (Basel), 8, 10.3390/cancers8100090 · DOI · Paper page
  7. Zhang, 2020, Photodynamic therapy as an alternative treatment in patients with invasive cutaneous SCC where surgery is not feasible: single center experience, Photodiagnosis Photodyn. Ther., 32, 10.1016/j.pdpdt.2020.101980 · DOI
  8. Keyal, 2019, Present and future perspectives of photodynamic therapy for cutaneous squamous cell carcinoma, J. Am. Acad. Dermatol., 80, 765, 10.1016/j.jaad.2018.10.042 · DOI
  9. Wang, 2018, Successful treatment of giant invasive cutaneous squamous cell carcinoma by plum-blossom needle assisted photodynamic therapy sequential with imiquimod: case experience, Photodiagnosis Photodyn. Ther., 21, 393, 10.1016/j.pdpdt.2017.12.010 · DOI
  10. Gilaberte, 2014, Cellular intrinsic factors involved in the resistance of squamous cell carcinoma to photodynamic therapy, J. Invest. Dermatol., 134, 2428, 10.1038/jid.2014.178 · DOI
  11. Lansbury, 2013, Interventions for non-metastatic squamous cell carcinoma of the skin: systematic review and pooled analysis of observational studies, BMJ, 347, f6153, 10.1136/bmj.f6153 · DOI
  12. Pines, 2014, Halofuginone for fibrosis, regeneration and cancer in the gastrointestinal tract, World J. Gastroenterol., 20, 14778, 10.3748/wjg.v20.i40.14778 · DOI
  13. Juarez, 2017, Halofuginone inhibits TGF-beta/BMP signaling and in combination with zoledronic acid enhances inhibition of breast cancer bone metastasis, Oncotarget, 8, 86447, 10.18632/oncotarget.21200 · DOI
  14. Tsuchida, 2017, Halofuginone enhances the chemo-sensitivity of cancer cells by suppressing NRF2 accumulation, Free Radic. Biol. Med., 103, 236, 10.1016/j.freeradbiomed.2016.12.041 · DOI
  15. Pines, 2008, Targeting TGFbeta signaling to inhibit fibroblast activation as a therapy for fibrosis and cancer: effect of halofuginone, Expert Opin. Drug Discov., 3, 11, 10.1517/17460441.3.1.11 · DOI
  16. McLaughlin, 2014, The chemistry and biology of febrifugine and halofuginone, Bioorg. Med. Chem., 22, 1993, 10.1016/j.bmc.2014.02.040 · DOI
  17. Endo, 2021, Targeting Nrf2-antioxidant signaling reverses acquired cabazitaxel resistance in prostate cancer cells, J. Biochem., 10.1093/jb/mvab025 · DOI
  18. Zeng, 2015, Rapamycin inhibits BAFF-stimulated cell proliferation and survival by suppressing mTOR-mediated PP2A-Erk1/2 signaling pathway in normal and neoplastic B-lymphoid cells, Cell. Mol. Life Sci., 72, 4867, 10.1007/s00018-015-1976-1 · DOI
  19. Gilbert, 2007, Incorporating photodynamic therapy into a medical and cosmetic dermatology practice, Dermatol. Clin., 25, 111, 10.1016/j.det.2006.09.012 · DOI
  20. Zhang, 2021, 5-Aminolaevulinic acid photodynamic therapy amplifies intense inflammatory response in the treatment of acne vulgaris via CXCL8, Exp. Dermatol., 10.1111/exd.14357 · DOI
  21. Ferino, 2020, The ROS-KRAS-Nrf2 axis in the control of the redox homeostasis and the intersection with survival-apoptosis pathways: implications for photodynamic therapy, J. Photochem. Photobiol. B, 202, 10.1016/j.jphotobiol.2019.111672 · DOI
  22. Tian, 2017, Enhancement of the effect of methyl pyropheophorbide-a-mediated photodynamic therapy was achieved by increasing ROS through inhibition of Nrf2-HO-1 or Nrf2-ABCG2 signaling, Anticancer Agents Med. Chem., 17, 1824
  23. Chen, 2019, Effects of low-dose ALA-PDT on fibroblast photoaging induced by UVA irradiation and the underlying mechanisms, Photodiagnosis Photodyn. Ther., 27, 79, 10.1016/j.pdpdt.2019.05.006 · DOI
  24. Cui, 2018, Nrf2 attenuates inflammatory response in COPD/emphysema: crosstalk with Wnt3a/beta-catenin and AMPK pathways, J. Cell. Mol. Med., 22, 3514, 10.1111/jcmm.13628 · DOI
  25. Bai, 2019, Sesamin enhances Nrf2-mediated protective defense against oxidative stress and inflammation in colitis via AKT and ERK activation, Oxid. Med. Cell Longev., 10.1155/2019/2432416 · DOI
  26. Gureev, 2020, Crosstalk between the mTOR and Nrf2/ARE signaling pathways as a target in the improvement of long-term potentiation, Exp. Neurol., 328, 10.1016/j.expneurol.2020.113285 · DOI

Metadata

Authors
Lv, T., Huang, J., Wu, M., Wang, H., Zeng, Q., & Wang, X.
Affiliations
  • Tongji University (CN)
  • Fudan University (CN)
Corresponding author
  • Wang, Hongwei
  • Zeng, Qingyu
  • Wang, Xiuli
ORCID
Venue
Photodiagnosis and Photodynamic Therapy
Publisher
Elsevier BV
Published
2022-03
Volume
37
Pages
102572
ISSN
1572-1000 (ISSN-L)
DOI
10.1016/j.pdpdt.2021.102572
OpenAlex
W3207705617
Cited by
16
References
35
Citations by year
2025: 6 · 2024: 6 · 2023: 1 · 2022: 3
FWCI
1.62
Type
journal article
Language
en
Update notices
erratum (2025-08-01)
Open access
closed
Licence
Locations
  • Photodiagnosis and Photodynamic Therapy (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Shanghai Municipal Health Commission (ZXYXZ-2019011)
  • Shanghai Municipal Natural Science Foundation (21ZR1457100)
  • National Natural Science Foundation of China (31801187, 82073013)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Photodynamic Therapy Research Studies
  • Health Sciences › Medicine › Dermatology › Nonmelanoma Skin Cancer Studies
  • Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
Keywords
halofuginone, 5-aminolevulinic acid photodynamic therapy, cutaneous squamous cell carcinoma, Nrf2 signaling, combination therapy, reactive oxygen species, apoptosis, cell migration, cell proliferation, c-Myc, Bcl-2, cyclin D1, ERK1/2, Akt, S6K1, β-catenin, tumor growth inhibition
MeSH terms
Aminolevulinic Acid, Animals, Carcinoma, Squamous Cell, Photochemotherapy, Piperidines, Skin Neoplasms, Apoptosis, Photosensitizing Agents, Cell Line, Tumor, NF-E2-Related Factor 2, Mice, Quinazolinones

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