title: In vitroAntiproliferative and Apoptosis Inducing Effect ofAllium atroviolaceumBulb Extract on Breast, Cervical, and Liver Cancer Cells.
abstract: Natural products are considered potent sources for novel drug discovery and development. The multiple therapeutic effects of natural compounds in traditional medicine motivate us to evaluate the cytotoxic activity of bulb ofAllium atroviolaceumin MCF7 and MDA-MB-231, HeLa and HepG2 cell lines. The bulb methanol extract ofA. atroviolaceumwas found to be an active cell proliferation inhibitor at the time and dose dependent manner. Determination of DNA content by flow cytometry demonstrated S and G2/M phase arrest of MCF-7 cell, correlated toCdk1downregulation, S phase arrest in MDA-MB-231 which is p53 andCdk1-dependent, sub-G0 cell cycle arrest in HeLa aligned withCdk1downregulation, G0/G1, S, G2/M phase arrest in HepG2 which is p53-dependent. Apoptosis as the mechanism of cell death was confirmed by morphology study, caspases activity assay, as well as apoptosis related gene expression,Bcl-2. Caspase-8, -9, and -3 activity with downregulation ofBcl-2illustrated occurrence of both intrinsic and extrinsic pathways in MCF7, while caspase-3 and -8 activity revealed extrinsic pathway of apoptosis, althoughBcl-2downregulated. In HeLa cells, the activity of caspase-9 and -3 and downregulation ofBcl-2shows intrinsic pathway or mitochondrial pathway, whereas HepG2 shows caspase independent apoptosis. Further, the combination of the extract with tamoxifen against MCF7 and MDA-MB-231 and combination with doxorubicin against HeLa and HeG2 demonstrated synergistic effect in most concentrations, suggests that the bulb ofA. atroviolaceummay be useful for the treatment of cancer lonely or in combination with other drugs.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Khazaei
authors.affiliation: Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia.
authors.forename: Norhaizan M
authors.initials: NM
authors.lastname: Esa
authors.affiliation: Malaysian Research Institute of Aging, Universiti Putra Malaysia Serdang, Malaysia.
authors.forename: Vasudevan
authors.initials: V
authors.lastname: Ramachandran
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia.
authors.forename: Roslida A
authors.initials: RA
authors.lastname: Hamid
authors.affiliation: Department of pharmacology, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Pandurangan
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia.
authors.forename: Ali
authors.initials: A
authors.lastname: Etemad
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia.
authors.forename: Patimah
authors.initials: P
authors.lastname: Ismail
keywords: Allium atroviolaceum; apoptosis; bulb; caspase; gene expression