{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:33:51Z","timestamp":1788878031046,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073464"],"award-info":[{"award-number":["82073464"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703098"],"award-info":[{"award-number":["81703098"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2020A15150875"],"award-info":[{"award-number":["2020A15150875"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2020A1515010275"],"award-info":[{"award-number":["2020A1515010275"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Photoderm Photoimm Photomed"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Human papillomavirus (HPV) infection and related diseases are difficult clinical challenges. The efficacy of 5\u2010aminolevulinic acid photodynamic therapy (ALA\u2010PDT) in treating condyloma acuminata is remarkable, with high virus clearance and low recurrence rates. Podophyllotoxin (POD) is the first\u2010line drug with a significant therapeutic effect on condyloma acuminata. However, no studies have determined whether POD\u2010combined ALA\u2010PDT improves high\u2010risk (HR)\u2010HPV\u2010infected cell killing. We aimed to investigate whether POD\u2010combined ALA\u2010PDT could promote HPV\u2010infected cell death more effectively than the single treatment and explore the underlying mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In HeLa and SiHa cells, flow cytometry, EdU assay and LDH release test were used to detect apoptosis, cell proliferation change and necrosis, respectively. To investigate whether the combined therapy might activate apoptosis and induce endoplasmic reticulum (ER) stress, flow cytometry was used to determine intracellular levels of ROS and calcium, and Western blotting was used to determine the expression of related proteins. Mitochondrial membrane depolarization was detected by JC\u20101 assay. Immunofluorescence staining and Western blotting were used to detect the activation of autophagy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Podophyllotoxin \u2010combined ALA\u2010PDT inhibited the proliferation and promoted apoptosis and necrosis more effectively than the single treatment at the same intensity and concentration. The activation of the caspase\u2010dependent apoptosis pathway, ER stress and autophagy was more substantial in POD\u2010combined ALA\u2010PDT than with single treatments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Podophyllotoxin \u2010combined ALA\u2010PDT effectively promoted cell death through several pathways in HeLa and SiHa cells. This combination might be a promising therapeutic strategy for the HR\u2010HPV infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/phpp.12754","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T04:20:02Z","timestamp":1636950002000},"page":"343-353","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Podophyllotoxin\u2010combined 5\u2010aminolevulinic acid photodynamic therapy significantly promotes HR\u2010HPV\u2010infected cell death"],"prefix":"10.1111","volume":"38","author":[{"given":"Jingying","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology, Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Department of Dermatology and Venereology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou 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