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.
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.
Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia; Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Aied M
AM
Alabsi
Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Kai Li
KL
Lim
Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Ian C
IC
Paterson
Faculty of Bioresource, University Sultan Zainal Abidin, Terengganu, Malaysia.
Rola
R
Ali-Saeed
Faculty of Pharmacy, Sana'a University, Sana'a, Yemen.
Bushra A
BA
Muharram
D017209:Apoptosis / Q000187:drug effects*; D001681:Biological Assay; D020169:Caspases / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D005591:Chemical Fractionation; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D031409:Dracaena / Q000737:chemistry*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D018307:Neoplasms, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D009707:Nucleosomes; D010718:Phosphatidylserines; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D045304:Cytochromes c; D020169:Caspases