title: Effect of thymol on peripheral blood mononuclear cell PBMC and acute promyelotic cancer cell line HL-60.
abstract: Thymol, a naturally occurring phenolic compound, has been known for its antioxidant, anti microbial, and anti inflammatory activity. Thymol has also been reported as anti-cancer agent, but its anti-cancer mechanism has not yet been fully elucidated. Thus, we aimed to investigate anticancer activity of thymol on HL-60 (acute promyelotic leukemia) cells. In our study, thymol demonstrated dose dependent cytotoxic effects on HL-60 cells after 24h of exposure. However, thymol did not show any cytotoxic effect in normal human PBMC. The cytotoxic effect of thymol on HL-60 cells appears to be associated with induction of cell cycle arrest at sub G0/G1 phase, and apoptotic cell death based on genomic DNA fragmentation pattern. Thymol also showed significant increase in production of reactive oxygen species (ROS) activity, increase in mitochondrial H(2)O(2) production and depolarization of mitochondrial membrane potential. On performing Western Blot analysis, thymol showed increase in Bax protein level with a concomitant decrease in Bcl2 protein expression in a dose dependent manner. Our study also showed activation of caspase -9, -8 and -3 and concomitant PARP cleavage, which is the hallmark of caspase-dependent apoptosis. Moreover, to rule out the involvement of other mechanisms in apoptosis induction by thymol, we also studied its effect on apoptosis inducing factor (AIF). Thymol induced AIF translocation from mitochondria to cytosol and to nucleus, thus indicating its ability to induce caspase independent apoptosis. We conclude that, thymol-induced apoptosis in HL-60 cells involves both caspase dependent and caspase independent pathways.
authors.affiliation: Environmental Health Division, National Environmental Engineering Research Institute, Nehru Marg, Nagpur, India. dipaduttadeb@gmail.com
authors.forename: Dipanwita Dutta
authors.initials: DD
authors.lastname: Deb
authors.forename: G
authors.initials: G
authors.lastname: Parimala
authors.forename: S
authors.initials: S
authors.lastname: Saravana Devi
authors.forename: Tapan
authors.initials: T
authors.lastname: Chakraborty
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D016193:G1 Phase; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D013943:Thymol / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D013943:Thymol; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9