{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T22:28:01Z","timestamp":1784068081497,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dr. Oxford Biotech Factory Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Renal cell carcinoma (RCC) presents significant therapeutic challenges due to its resistance to conventional treatments. Natural compounds with photodynamic properties, such as chlorophyll derivatives, offer potential for novel interventions. This study investigates the apoptotic effects of a chlorophyll-enriched green propolis compound activated by daylight-mediated photodynamic therapy (PDT) on RCC cells. A novel compound formulated from standardized ethanol extracts of Taiwanese green propolis, wheatgrass, and mulberry leaves was characterized using high-performance liquid chromatography (HPLC). Human RCC 786-O cells were treated with varying concentrations of the compound, with or without daylight PDT (570 nm). Cell viability was assessed via MTT assay, and median effective concentrations (EC50) were calculated. HPLC analysis identified Artepillin C as the major constituent. The compound induced dose-dependent cytotoxicity, which was significantly enhanced by daylight PDT. EC50 values dropped from 3.027 \u00b5L (compound alone) to 1.728 \u00b5L (with PDT), indicating synergistic efficacy. Cell viability significantly decreased in PDT-treated cells compared to non-treated controls (p &lt; 0.05) indicating apoptosis. Daylight-activated PDT significantly amplifies the anticancer efficacy of the compound against RCC cells. Preliminary data suggest the potential of chlorophyll-enriched green propolis photodynamic activation (GPDT) as a natural adjunctive strategy for RCC, warranting further in vivo investigation.<\/jats:p>","DOI":"10.3390\/ijms26146897","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T11:12:34Z","timestamp":1752837154000},"page":"6897","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Photodynamic Activation of a Novel Chlorophyll-Enriched Green Propolis Compound Triggers Apoptosis in Renal Cell Carcinoma"],"prefix":"10.3390","volume":"26","author":[{"given":"Yao-Kuan","family":"Chen","sequence":"first","affiliation":[{"name":"Dr. Oxford Biotech Factory Co., Ltd., Taichung 407, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Min","family":"Chiu","sequence":"additional","affiliation":[{"name":"Dr. Oxford Biotech Factory Co., Ltd., Taichung 407, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-Yi","family":"Huang","sequence":"additional","affiliation":[{"name":"Oxperial Biohealth Ltd., Oxford OX2 6HT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ta-Chun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Tzu-Hsuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Nuffield Department of Primary Care Health Science, University of Oxford, Oxford OX2 6GG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3322\/caac.21208","article-title":"Cancer statistics, 2014","volume":"64","author":"Siegel","year":"2014","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.6004\/jnccn.2022.0001","article-title":"Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology","volume":"20","author":"Motzer","year":"2022","journal-title":"J. Natl. Compr. Canc Netw."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3109\/19390211.2015.1008614","article-title":"Emerging Adjuvant Therapy for Cancer: Propolis and its Constituents","volume":"13","author":"Patel","year":"2016","journal-title":"J. Diet. Suppl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"19610","DOI":"10.3390\/molecules191219610","article-title":"Recent Advances in the Chemical Composition of Propolis","volume":"19","author":"Huang","year":"2014","journal-title":"Molecules"},{"key":"ref_5","first-page":"76","article-title":"Propolis: An update on its chemical diversity, botanical origin and biological activities","volume":"2","author":"Ghallab","year":"2025","journal-title":"J. Adv. Pharm. Sci."},{"key":"ref_6","first-page":"22","article-title":"Biological activity of bee propolis in health and disease","volume":"7","author":"Khalil","year":"2006","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1051\/apido:2000102","article-title":"Propolis: Recent advances in chemistry and plant origin","volume":"31","author":"Bankova","year":"2000","journal-title":"Apidologie"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Huang, W.-D., Peng, S.-F., Tsao, N.-W., Wang, S.-Y., Tzeng, S.-L., and Hu, N.-J. (2025). Taiwan Green Propolis Nanoparticles Induce Antiproliferation and Apoptosis in Oral Cancer Cells. Biomedicines, 13.","DOI":"10.3390\/biomedicines13040921"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.5603\/FHC.2012.0004","article-title":"The anticancer activity of propolis","volume":"50","author":"Sawicka","year":"2012","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.biopha.2005.03.013","article-title":"Antitumor, hematostimulative and radioprotective action of water-soluble derivative of propolis (WSDP)","volume":"59","year":"2005","journal-title":"Biomed. Pharmacother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3784092","DOI":"10.1155\/2024\/3784092","article-title":"Black Mulberry (Morus nigra L.): A Review of Attributes as an Anticancer Agent to Encourage Pharmaceutical Development","volume":"2024","author":"Ferraz","year":"2024","journal-title":"Adv. Pharmacol. Pharm. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tamraz, M., Al Ghossaini, N., and Temraz, S. (2024). The Role of Wheatgrass in Colorectal Cancer: A Review of the Current Evidence. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105166"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.pdpdt.2019.04.033","article-title":"Photodynamic therapy for cancer: Role of natural products","volume":"26","author":"Mansoori","year":"2019","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.2174\/138955751512150731112836","article-title":"The Medical Use of Wheatgrass: Review of the Gap Between Basic and Clinical Applications","volume":"15","author":"Cohen","year":"2015","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_15","first-page":"ZC40","article-title":"Wheatgrass: Green Blood can Help to Fight Cancer","volume":"11","author":"Gore","year":"2017","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.jfda.2017.12.007","article-title":"Mulberry leaf extract inhibit hepatocellular carcinoma cell proliferation via depressing IL-6 and TNF-\u03b1 derived from adipocyte","volume":"26","author":"Chang","year":"2018","journal-title":"J. Food Drug Anal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1900132","DOI":"10.1002\/adhm.201900132","article-title":"Photosensitizers for Photodynamic Therapy","volume":"8","author":"Lan","year":"2019","journal-title":"Adv. Healthc. Mater."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sulaiman, C., George, B.P., Balachandran, I., and Abrahamse, H. (2022). Photoactive Herbal Compounds: A Green Approach to Photodynamic Therapy. Molecules, 27.","DOI":"10.3390\/molecules27165084"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1111\/j.1468-3083.2011.04386.x","article-title":"Daylight photodynamic therapy for actinic keratosis: An international consensus: International Society for Photodynamic Therapy in Dermatology","volume":"26","author":"Wiegell","year":"2012","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kubrak, T.P., Ko\u0142odziej, P., Sawicki, J., Mazur, A., Koziorowska, K., and Aebisher, D. (2022). Some Natural Photosensitizers and Their Medicinal Properties for Use in Photodynamic Therapy. Molecules, 27.","DOI":"10.3390\/molecules27041192"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2464491","DOI":"10.1080\/20565623.2025.2464491","article-title":"Novel compounds of Taiwanese green propolis induce apoptosis of human glioblastoma cells by daylight photodynamic action","volume":"11","author":"Chen","year":"2025","journal-title":"Future Sci. OA"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Forma, E., and Bry\u015b, M. (2021). Anticancer Activity of Propolis and Its Compounds. Nutrients, 13.","DOI":"10.3390\/nu13082594"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.2174\/1871520618666180604092930","article-title":"Artepillin C Induces Selective Oxidative Stress and Inhibits Migration and Invasion in a Comprehensive Panel of Human Cervical Cancer Cell Lines","volume":"18","author":"Souza","year":"2018","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.lfs.2004.07.019","article-title":"Chilean propolis: Antioxidant activity and antiproliferative action in human tumor cell lines","volume":"76","author":"Russo","year":"2004","journal-title":"Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rivera-Ya\u00f1ez, N., Ruiz-Hurtado, P.A., Rivera-Ya\u00f1ez, C.R., Arciniega-Mart\u00ednez, I.M., Yepez-Ortega, M., Mendoza-Arroyo, B., Rebollar-Ru\u00edz, X.A., M\u00e9ndez-Cruz, A.R., Res\u00e9ndiz-Albor, A.A., and Nieto-Ya\u00f1ez, O. (2023). The Role of Propolis as a Natural Product with Potential Gastric Cancer Treatment Properties: A Systematic Review. Foods, 12.","DOI":"10.3390\/foods12020415"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.biopha.2016.04.007","article-title":"Photodynamic efficiency of a chlorophyll-a derivative in vitro and in vivo","volume":"81","author":"Zhang","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Heo, S.-Y., Lee, Y., Kim, T.-H., Heo, S.-J., Shin, H., Lee, J., Yi, M., Kang, H.W., and Jung, W.-K. (2023). Anti-Cancer Effect of Chlorophyllin-Assisted Photodynamic Therapy to Induce Apoptosis through Oxidative Stress on Human Cervical Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411565"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"434","DOI":"10.7150\/thno.67300","article-title":"Recent advances in nanomedicines for photodynamic therapy (PDT)-driven cancer immunotherapy","volume":"12","author":"Ji","year":"2022","journal-title":"Theranostics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.canlet.2006.01.016","article-title":"Apoptosis of human melanoma cells induced by the novel compounds propolin A and propolin B from Taiwenese propolis","volume":"245","author":"Chen","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/978-1-61779-080-5_20","article-title":"Cell sensitivity assays: The MTT assay","volume":"731","author":"Kaspers","year":"2011","journal-title":"Methods Mol. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6897\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:11:52Z","timestamp":1760033512000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,18]]},"references-count":30,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26146897"],"URL":"https:\/\/doi.org\/10.3390\/ijms26146897","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,18]]}}}