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Molecules 2017, 22(5), 732; doi:10.3390/molecules22050732

Brazilian Green Propolis Extract Synergizes with Protoporphyrin IX-mediated Photodynamic Therapy via Enhancement of Intracellular Accumulation of Protoporphyrin IX and Attenuation of NF-κB and COX-2

1
School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
2
School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China
3
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China
4
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
5
Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China
6
Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China
These authors contributed equally to this work and should be considered co-first authors.
*
Authors to whom correspondence should be addressed.
Academic Editor: Thomas J. Schmidt
Received: 7 March 2017 / Revised: 25 April 2017 / Accepted: 28 April 2017 / Published: 4 May 2017
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Abstract

Brazilian green propolis (BGP) is noted for its impressive antitumor effects and has been used as a folk medicine in various cultures for many years. It has been demonstrated that BGP could enhance the cytotoxic effect of cytostatic drugs on tumor cells. Photodynamic therapy (PDT) is a therapeutic approach used against malignant cells. To assess the synergistic effect of BGP extract on protoporphyrin IX (PpIX)-mediated photocytotoxicity, MTT assays were performed using A431 and HeLa cells. TUNEL assay and Annexin V-FITC/PI staining were performed to confirm the induction of apoptosis. Western blotting analysis was performed to examine the pro-apoptotic proteins, anti-apoptotic proteins and inflammation related proteins in A431 cells. Intracellular accumulation of PpIX was examined by flow cytometry. The synergistic effect of BGP extract in PpIX-PDT was also evaluated with a xenograft model. Our findings reveal that BGP extract increased PpIX-mediated photocytotoxicity in A431 and HeLa cells. PpIX-PDT with BGP extract treatment resulted in a decrease in Bcl-xL and an increase in NOXA, Bax and caspase-3 cleavage. The protein expression levels of p-IKKα/β, NF-κB and COX-2 were upregulated by PpIX-PDT but significantly attenuated when in combination with BGP extract. BGP extract was also found to significantly enhance the intracellular accumulation of PpIX in A431 cells. BGP extract increased PpIX-mediated photocytotoxicity in a xenograft model as well. Our findings provide evidence for a synergistic effect of BGP extract in PpIX-PDT both in vitro and in vivo. View Full-Text
Keywords: Brazilian green propolis; synergy; photodynamic therapy; cancer; inflammation; apoptosis Brazilian green propolis; synergy; photodynamic therapy; cancer; inflammation; apoptosis
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MDPI and ACS Style

Wang, C.-C.; Wang, Y.-X.; Yu, N.-Q.; Hu, D.; Wang, X.-Y.; Chen, X.-G.; Liao, Y.-W.; Yao, J.; Wang, H.; He, L.; Wu, L. Brazilian Green Propolis Extract Synergizes with Protoporphyrin IX-mediated Photodynamic Therapy via Enhancement of Intracellular Accumulation of Protoporphyrin IX and Attenuation of NF-κB and COX-2. Molecules 2017, 22, 732.

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