Cell Cycle Arrest and Apoptosis Induction via Modulation of Mitochondrial Integrity by Bcl-2 Family Members and Caspase Dependence in Dracaena cinnabari -Treated H400 Human Oral Squamous Cell Carcinoma
Document Type
Article
Publication Date
1-1-2016
Abstract
Dracaena cinnabari Balf.f. is a red resin endemic to Socotra Island, Yemen. Although there have been several reports on its therapeutic properties, information on its cytotoxicity and anticancer effects is very limited. This study utilized a bioassay-guided fractionation approach to determine the cytotoxic and apoptosis-inducing effects of D. cinnabari on human oral squamous cell carcinoma (OSCC). The cytotoxic effects of D. cinnabari crude extract were observed in a panel of OSCC cell lines and were most pronounced in H400. Only fractions DCc and DCd were active on H400 cells; subfractions DCc15 and DCd16 exhibited the greatest cytotoxicity against H400 cells and D. cinnabari inhibited cells proliferation in a time-dependent manner. This was achieved primarily via apoptosis where externalization of phospholipid phosphatidylserine was observed using DAPI/Annexin V fluorescence double staining mechanism studied through mitochondrial membrane potential assay cytochrome c enzyme-linked immunosorbent and caspases activities revealed depolarization of mitochondrial membrane potential (MMP) and significant activation of caspases 9 and 3/7, concomitant with S phase arrest. Apoptotic proteins array suggested that MMP was regulated by Bcl-2 proteins family as results demonstrated an upregulation of Bax, Bad, and Bid as well as downregulation of Bcl-2. Hence, D. cinnabari has the potential to be developed as an anticancer agent.
Keywords
Antineoplastic agent, Caspase, Caspase 3, Caspase 7, Caspase 8, Caspase 9, Cisplatin, Cytochrome c, DNA fragment, Dracaena cinnabari extract, Phosphatidylserine, Plant extract, Protein BAD, Protein Bax, Protein bcl 2, Protein Bid, Tumor necrosis factor related apoptosis inducing ligand, Unclassified drug, Caspase, Cytochrome c, Nucleosome, Phosphatidylserine, Plant extract, Protein bcl 2
Divisions
Dentistry
Funders
University of Malaya, Malaysia: UMRG RP002D-13HTM and RG422/12HTM
Publication Title
BioMed Research International
Volume
2016
Publisher
Hindawi Publishing Corporation