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

Autor: Chengcheng Wang, He Ling, Yuxuan Wang, Liao Youwei, Chen Xingguang, Jing Yao, Nian-Qin Yu, Hu Die, Xiaoyan Wang, Wang Hao, Liang Wu
Rok vydání: 2017
Předmět:
0301 basic medicine
medicine.medical_treatment
Pharmaceutical Science
Protoporphyrins
synergy
Photodynamic therapy
Analytical Chemistry
HeLa
chemistry.chemical_compound
0302 clinical medicine
Annexin
Drug Discovery
Brazilian green propolis
photodynamic therapy
cancer
inflammation
apoptosis
Chromatography
High Pressure Liquid
Mice
Inbred BALB C
Protoporphyrin IX
NF-kappa B
Drug Synergism
Flow Cytometry
Biochemistry
Chemistry (miscellaneous)
030220 oncology & carcinogenesis
Molecular Medicine
Heterografts
A431 cells
Brazil
Mice
Nude
Biology
Propolis
Article
lcsh:QD241-441
03 medical and health sciences
lcsh:Organic chemistry
In vivo
Cell Line
Tumor
medicine
Animals
Humans
Physical and Theoretical Chemistry
Organic Chemistry
biology.organism_classification
In vitro
030104 developmental biology
chemistry
Photochemotherapy
Apoptosis
Cyclooxygenase 2
Cancer research
Spectrophotometry
Ultraviolet
Zdroj: Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
Molecules, Vol 22, Iss 5, p 732 (2017)
Molecules; Volume 22; Issue 5; Pages: 732
ISSN: 1420-3049
Popis: 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.
Databáze: OpenAIRE
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