Proanthocyanidins from Uncaria rhynchophylla induced apoptosis in MDA-MB-231 breast cancer cells while enhancing cytotoxic effects of 5-fluorouracil. (September 2017)

• Record Type: Journal Article
• Authors: Chen, Xiao-Xin; Leung, George Pak-Heng; Zhang, Zhang-Jin; Xiao, Jian-Bo; Lao, Li-Xing; Feng, Feng; Mak, Judith Choi-Wo; Wang, Ying; Sze, Stephen Cho-Wing; Zhang, Kalin Yan-Bo
• Is Part Of: Food and chemical toxicology. Volume 107:Part A(2017)
• Page Start: 248
• Page End: 260
• Publication Date: 2017-09
• Subjects: Uncaria rhynchophylla -- Proanthocyanidins -- 5-Fluorouracil -- Breast cancer -- Apoptosis; AAE/g dw ascorbic acid equivalent/g dry weight -- ABTS 2, 20-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid -- CI combination index -- CIwt weighted average -- DCF-DA 2′, 7′-dichlorofluorescin diacetate -- Dm the dose that produces 50 percent effect -- DMEM Dulbecco's Modified Eagle Medium -- DPPH 2, 2-diphenyl-1-picrylhydrazyl -- DP degree of polymerization -- DRI drug reduction index -- 5-FU 5-fluorouracil -- Fa Factional affected -- FBS fetal bovine serum -- Fu Factional unaffected -- FRAP ferric reducing antioxidant power -- GAE/g dw gallic acid equivalent/g dry weight -- HPLC-DAD-ESI-MS/MS high performance liquid chromatography/diode array detector coupled with electrospray ionization tandem mass spectrometry -- ROS reactive oxygen species -- HRF Heterocyclic ring fission -- IC50 the dose that inhibit 50 percent activity -- m the shape parameter for the dose-effect curve which is the slope of the median-effect plot -- MALDI-TOF MS matrix-assisted laser desorption/ionization time-of-flight mass spectrometry -- MMP mitochondrial membrane potential -- MTT 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- PBS phosphate buffer solution -- PI propidium iodide -- QM Quinine methide -- r value the linear correlation coefficient of the median-effect plot -- Rh123 Rhodamine 123 -- TFA trifluoroacetic acid -- UPAs proanthocyanidins from Uncaria rhynchophylla; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2017.07.012
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Breast cancer is the most frequently diagnosed cancer and cause of cancer death in women worldwide. Current treatments often result in systematic toxicity and drug resistance. Combinational use of non-toxic phytochemicals with chemotherapeutic agents to enhance the efficacy and reduce toxicity would be one promising approach. In this study, bioactive proanthocyanidins from Uncaria rhynchophylla (UPAs) were isolated and their anti-breast cancer effects alone and in combination with 5- fluorouracil (5-FU) were investigated in MDA-MB-231 breast cancer cells. The results showed that UPAs significantly inhibited cell viability and migration ability in a dose-dependent manner. Moreover, UPAs induced apoptosis in a dose-dependent manner which was associated with increased cellular reactive oxygen species production, loss of mitochondrial membrane potential, increases of Bax/Bcl-2 ratio and levels of cleaved caspase 3. Treatments of the cells with UPAs resulted in an increase in G2/M cell cycle arrest. Cytotoxic effects of 5-FU against MDA-MB-231 cells were enhanced by UPAs. The combination treatment of UPAs and 5-FU for 48 h elicited a synergistic cytotoxic effect on MDA-MB-231 cells. Altogether, these data suggest that UPAs are potential therapeutic agents for breast cancer. Graphical abstract: Highlights: UPAs were mixtures of homo- and heteropolymers of A and B-type propelargonidin, procyanidins, and prodelphinidins. UPAs significantly inhibited MDA-MB-231 cell viability and migration ability in a dose-dependent manner in vitro . UPAs induced oxidative stress and intrinsic apoptosis. Combination treatment of UPAs and 5-FU for 48h elicited a synergistic cytotoxic effect.