title: Tanacetum polycephalum (L.) Schultz-Bip. induces mitochondrial-mediated apoptosis and inhibits migration and invasion in MCF7 cells.
abstract: Tanacetum polycephalum (L.) Schultz-Bip (Mokhaleseh) has been traditionally used in the treatment of headaches, migraines, hyperlipidemia and diabetes. The present study aimed to evaluate its anticancer properties and possible mechanism of action using MCF7 as an in vitro model. T. polycephalum leaves were extracted using hexane, chloroform and methanol solvents and the cytotoxicity was evaluated using the MTT assay. Detection of the early apoptotic cells was investigated using acridine orange/propidium iodide staining. An Annexin-V-FITC assay was carried out to observe the phosphatidylserine externalization as a marker for apoptotic cells. High content screening was applied to analyze the cell membrane permeability, nuclear condensation, mitochondrial membrane potential (MMP) and cytochrome c release. Apoptosis was confirmed by using caspase-8, caspase-9 and DNA laddering assays. In addition, Bax/Bcl-2 expressions and cell cycle arrest also have been investigated. MTT assay revealed significant cytotoxicity of T. Polycephalum hexane extract (TPHE) on MCF7 cells with the IC50 value of 6.42±0.35 µg/mL. Significant increase in chromatin condensation was also observed via fluorescence analysis. Treatment of MCF7 cells with TPHE encouraged apoptosis through reduction of MMP by down-regulation of Bcl-2 and up-regulation of Bax, triggering the cytochrome c leakage from mitochondria to the cytosol. The treated MCF7 cells significantly arrested at G1 phase. The chromatographic analysis elicited that the major active compound in this extract is 8β-hydroxy-4β,15-dihydrozaluzanin C. Taken together, the results presented in this study demonstrated that the hexane extract of T. Polycephalum inhibits the proliferation of MCF7 cells, resulting in the cell cycle arrest and apoptosis, which was explained to be through the mitochondrial pathway.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. hamed_karimian61@yahoo.com.
authors.forename: Hamed
authors.initials: H
authors.lastname: Karimian
authors.affiliation: Medical Research Centre, Jazan University, Jazan 2092, Saudi Arabia. syammohanm@yahoo.com.
authors.forename: Syam
authors.initials: S
authors.lastname: Mohan
authors.affiliation: Biomolecular Research Group, Biochemistry Program, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia. soheil.zorofchian@gmail.com.
authors.forename: Soheil Zorofchian
authors.initials: SZ
authors.lastname: Moghadamtousi
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia. mehranfadaie_n@yahoo.com.
authors.forename: Mehran
authors.initials: M
authors.lastname: Fadaeinasab
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. mahbobehrazavi@gmail.com.
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Razavi
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. aditya@um.edu.my.
authors.forename: Aditya
authors.initials: A
authors.lastname: Arya
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. behnam@um.edu.my.
authors.forename: Behnam
authors.initials: B
authors.lastname: Kamalidehghan
authors.affiliation: Medical Research Centre, Jazan University, Jazan 2092, Saudi Arabia. hapipah@um.edu.my.
authors.forename: Hapipah Mohd
authors.initials: HM
authors.lastname: Ali
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. ibrahimn@um.edu.my.
authors.forename: Mohamad Ibrahim
authors.initials: MI
authors.lastname: Noordin
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002463:Cell Membrane Permeability; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation; D002470:Cell Survival; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009361:Neoplasm Invasiveness; D031203:Tanacetum / Q000737:chemistry*; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins