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Fisetin and polymeric micelles encapsulating fisetin exhibit potent cytotoxic effects towards ovarian cancer cells

Author:
Xiao, Xue, Zou, Juan, Fang, Yin, Meng, Yibo, Xiao, Chao, Fu, Jiaxin, Liu, Shiyu, Bai, Peng, Yao, Yuan
Source:
BMC complementary and alternative medicine 2018 v.18 no.1 pp. 91
ISSN:
1472-6882
Subject:
Western blotting, alternative medicine, angiogenesis, animal models, antineoplastic activity, apoptosis, color, cytotoxicity, dose response, encapsulation, flow cytometry, hydrophilicity, immunohistochemistry, mice, micelles, neoplasm cells, ovarian neoplasms, pharmaceutical industry, ultrasonography
Abstract:
BACKGROUND: The anti-tumor activities of Natural compounds and their derivatives are of great interest to pharmaceutical industries. Fisetin is one of prospective natural compounds in this regard but unfortunately with poor hydrophilicity. METHODS: The effects of unmodified and modified fisetin in cultured ovarian cancer cells were compared by transmission electronmicroscopy to determine apoptotic bodies, MTT assay to quantitate cell numbers, and fluorescence activated cell sorting analyse of various markers to determine the apoptotic state. In addition, the efficacy of fisetin and fisetin-micelles in vivo was determined by using immunocompromised mice. Apoptosis was measured by established markers using both western blot analysis and immunochemistry. Angiogenesis in a xenograft mouse model carring SKOV3 cells was evaluated by color Doppler ultrasound and immunohistochemistry. RESULT: Multiple lines of evidence indicated that fisetin and fisetin micelles induce apoptosis in ovarian cancer cells in a dose-dependent manner. Histological analysis, terminal deoxynucleotidyltransferase-mediated nick-end labeling assay, western blot, immunohistochemical detection and microvessel density detection demonstrated that fisetin and fisetin micelles induced increased tumor apoptosis, proliferation suppression and antiangiogenesis activities. CONCLUSION: As far as we know, the present study is the first time to demonstrate the potency of both fisetin and fisetin micelles inducing apoptosis in ovarian cancer cells. Further studies will be needed to validate the therapeutic potential of fisetin and fisetin micelles in ovarian cancer treatment.
Agid:
5911811