title: Jolkinolide B induces apoptosis in MDA-MB-231 cells through inhibition             of the PI3K/Akt signaling pathway.
abstract: The phosphoinositol-3-kinase (PI3K)/Akt signal transduction pathway is critically             important for tumor cell growth, proliferation and apoptosis. Apoptosis activation             has been reported to be a good target in cancer therapies. In this study, we have             found that jolkinolide B (JB), a diterpenoid from the traditional Chinese medicinal             herb Euphorbia fischeriana Steud, strongly inhibited the expression of the PI3K             p85 subunit and the phosphorylation of Akt. Furthermore, we evaluated the effects             of JB on the proliferation and apoptosis of MDA-MB-231 human breast cancer cells.             Our results show significant induction of apoptosis in MDA-MB-231 cells incubated             with JB. This effect was enhanced by combination with LY294002. In addition, treatment             with JB could induce downregulation of the Bcl-2/Bax ratio, and subsequent promotion             of mitochondrial release of cytochrome c and activation of caspase-3. Taken together,             JB-induced apoptosis of MDA-MB-231 cells occurs through the mitochondrial pathway.             Further, the PI3K/Akt signaling cascade plays a role in the induction of apoptosis             in JB-treated cells. These observations suggest that JB may have therapeutic applications             in the treatment of cancer.
authors.affiliation: Department of Pharmacology, Qiqihar Medical University, Qiqihar 161006, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lin
authors.forename: Hongxia
authors.initials: H
authors.lastname: Cui
authors.forename: Huiyu
authors.initials: H
authors.lastname: Xu
authors.forename: Liling
authors.initials: L
authors.lastname: Yue
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Liyan
authors.initials: L
authors.lastname: Jiang
authors.forename: Jicheng
authors.initials: J
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms; D053148:Caspase 3 / Q000096:biosynthesis / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D053148:Caspase 3; D002867:Chromones; D045304:Cytochromes c; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D009025:Morpholines; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C057914:jolkinolide B