Inhibitory Kinetics and Mechanism of Flavonoids Extracted from Cotinus coggygria Scop. Against Glioblastoma Cancer.
This proposal seeks to study the potential therapeutic modality of chemoprevention and anticancer effects and mechanisms of the flavonoids from Cotinus coggygria Scop. on glioblastoma cancer. In the current study, the total flavonoids (TFs) isolated from Cotinus coggygria Scop. var. cinerea Engl. (Cotinus coggygria Scop.) and the major flavonoids of Cotinus coggygria Scop. (CCFs) were identified, and the inhibitory kinetics of TF and CCF on glioblastoma cell lines were calculated. We also investigated whether TF or CCF regulated the apoptotic mechanism in cellular models of glio-blastoma cells. Finally, we evaluated whether treatment with TF or CCF suppressed tumor growth and inhibited migration in orthotopic mouse models of glioblastoma in vivo. In this study, the CCFs were identified as rutin, myricetin, and fisetin. TF and CCF remarkably inhibited cell proliferation and downregulated the PI3K/Akt and ERK signaling pathway in glioblastoma cell lines. Furthermore, the mitochondrial caspase-dependent cascade was regulated by TF and myricetin. In addition, TF and myricetin exhibited significant antitumor effects on glioblastoma in vivo. Taken together, these results suggest that phytochemical and biological data provide evidence for the active components in Cotinus coggygria, and that the TFs are responsible for the anticancer effects on glioblastoma cell growth via induction of apoptosis. In addition, the representative compound myricetin could provide a clinically relevant therapeutic opportunity. Therefore, our data strongly suggest that myricetin-deprived CCF can serve as a potent chemopreventive herbal medicine.
a Department of Pharmaceutics , Shanghai Eighth People's Hospital, Jiangsu University , Shanghai , China.
Gang
G
Wang
a Department of Pharmaceutics , Shanghai Eighth People's Hospital, Jiangsu University , Shanghai , China.|b Hubei University of Medicine , Shiyan , Hubei , China.
Jun-Jie
JJ
Wang
a Department of Pharmaceutics , Shanghai Eighth People's Hospital, Jiangsu University , Shanghai , China.
Li
L
Du
a Department of Pharmaceutics , Shanghai Eighth People's Hospital, Jiangsu University , Shanghai , China.
Li
L
Fei
c Department of Health Technology and Informatics , The Hong Kong Polytechnic University , Hong Kong.
Shing-Shun Tony
ST
To
D027926:Anacardiaceae / Q000737:chemistry*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D007700:Kinetics; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D051057:Proto-Oncogene Proteins c-akt