title: Molecular mechanism of apoptosis induction by Gaillardin, a sesquiterpene lactone, in breast cancer cell lines : Gaillardin-induced apoptosis in breast cancer cell lines.
abstract: Medicinal plant extracts have been widely used for cancer treatment. Gaillardin is a natural sesquiterpene lactone that has recently been reported to have anticancer properties. The ability to induce apoptosis is an important property of a candidate anticancer drug, which discriminates between anticancer drugs and toxic compounds. The current study was therefore carried out to address the issue if Gaillardin is able to induce apoptosis in the breast cancer cell lines MCF-7 and MDA-MB-468 and to determine the underlying mechanism of its anticancer effects. Apoptosis induction by Gaillardin treatment was confirmed by annexin V-FITC/PI staining, and caspase-3,-6, and-9 activation. Using Western blot analysis, we found that Gaillardin upregulated the pro-apoptotic protein Bax and p53 and downregulated the anti-apoptotic protein Bcl-2. Moreover, the apoptotic effect of Gaillardin was also related to ROS production and loss of mitochondrial membrane potential (ΔΨm). Taken together, these results demonstrate that Gaillardin can inhibit proliferation of breast cancer cells via inducing mitochondrial apoptotic pathway and therefore, might be a promising molecule in cancer chemoprevention or chemotherapy.
authors: Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
authors: Faranak
authors: F
authors: Fallahian
authors: Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
authors: Mahmoud
authors: M
authors: Aghaei
authors: Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
authors: Mohammad Hossein
authors: MH
authors: Abdolmohammadi
authors: Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. mhmoghadam@sbmu.ac.ir.|Traditional Medicine and Materia Medica Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. mhmoghadam@sbmu.ac.ir.
authors: Maryam
authors: M
authors: Hamzeloo-Moghadam
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053178:Caspase 6 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D038143:Inula / Q000737:chemistry*; D007492:Iran; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010946:Plants, Medicinal; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C000595707:BCL2 protein, human; D007783:Lactones; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D051028:bcl-2-Associated X Protein; C476872:gaillardin; C505407:CASP3 protein, human; C505514:CASP6 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053178:Caspase 6; D053453:Caspase 9
keywords: Apoptosis; Breast cancer; Gaillardin; Mitochondrial pathway; Sesquiterpene lactone