title: Wogonin induces apoptosis and down-regulates survivin in human breast cancer MCF-7 cells by modulating PI3K-AKT pathway.
abstract: Wogonin, one of flavonoid compounds isolated from Chinese herbal plants Scutellaria baicalensis Georgi, has been recognized as a potent anti-cancer agent acting through control of growth, differentiation and apoptosis. However, the underlying molecular mechanism of its anti-cancer activity remains to be further elucidated. In this study, we investigated the potential role of wogonin in the induced-apoptosis of human breast cancer cells MCF-7. Wogonin was found to inhibit the proliferation of MCF-7 in a concentration and time-dependent manner, notably wogonin could induce G1 phase arrest of MCF-7 cells. Wogonin-induced apoptosis was accompanied by a significant decrease of the Bcl-2 and survivin and increase of Bax and p53. Wogonin also increased active apoptosis forms of caspases-3, -8, -9 significantly. Z-DEVD-fmk, a specific caspase-3 inhibitor, significantly inhibited wogonin-induced cell apoptosis. Wogonin also suppressed the phosphorylation of PI3K/Akt and induced phosphorylation of ERK. PD98059, a specific ERK inhibitor, significantly blocked wogonin-induced apoptosis. On the other hand, LY294002, a specific PI3K inhibitor, significantly increased wogonin-induced cell apoptosis. Further study indicated that LY294002 not only down-regulated the expression of survivin alone, but also enhanced the inhibition of survivin expression combined with wogonin. In conclusion, the pro-apoptotic effect of wogonin is mediated through the activation of ERK and the activation of caspases, and is correlated with the block of the PI3K/Akt/survivin signal pathways in MCF-7 cells.
authors.affiliation: Institute of Molecular Medicine, Huaqiao University, Quanzhou, 362021, China. hkf5306@163.com
authors.forename: K F
authors.initials: KF
authors.lastname: Huang
authors.forename: G D
authors.initials: GD
authors.lastname: Zhang
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Diao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D005419:Flavonoids; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases; C085514:wogonin