title: Plumbagin alters telomere dynamics, induces DNA damage and cell death in human brain tumour cells.
abstract: Natural plant products may possess much potential in palliative therapy and supportive strategies of current cancer treatments with lesser cytotoxicity to normal cells compared to conventional chemotherapy. In the current study, anti-cancer properties of plumbagin, a plant-derived naphthoquinone, on brain cancer cells were determined. Plumbagin treatment resulted in the induction of DNA damage, cell cycle arrest and apoptosis, followed by suppression of the colony forming ability of the brain tumour cells. These effects were substantiated by upregulation of PTEN, TNFRSF1A and downregulation of E2F1 genes, along with a drop in MDM2, cyclin B1, survivin and BCL2 protein expression. Plumbagin induced elevated levels of caspase-3/7 activity as well. For the first time, we show here that plumbagin inhibits telomerase in brain tumour cells and results in telomere shortening following chronic long-term treatment. This observation implies considerable cytotoxicity of plumbagin towards cancer cells with higher telomerase activity. Collectively, our findings suggest plumbagin as a potential chemotherapeutic phytochemical in brain tumour treatment modalities.
authors.affiliation: Genome Stability Laboratory, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Aik Kia
authors.initials: AK
authors.lastname: Khaw
authors.affiliation: Genome Stability Laboratory, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Safoura
authors.initials: S
authors.lastname: Sameni
authors.affiliation: Genome Stability Laboratory, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Shriram
authors.initials: S
authors.lastname: Venkatesan
authors.affiliation: Genome Stability Laboratory, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Division of Clinical Embryology, Department of Obstetrics and Gynaecology, Kasturba Medical College, Manipal University, Manipal, 576104, India.
authors.forename: Guruprasad
authors.initials: G
authors.lastname: Kalthur
authors.affiliation: Genome Stability Laboratory, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Tembusu College, National University of Singapore, Singapore 138597, Singapore. Electronic address: phsmph@nus.edu.sg.
authors.forename: M Prakash
authors.initials: MP
authors.lastname: Hande
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D009285:Naphthoquinones / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics; D016615:Telomere / Q000187:drug effects*; D059506:Telomere Shortening
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones; D019098:Telomerase; C014758:plumbagin
keywords: Cancer therapeutics; Cell death; DNA damage; Plumbagin; Telomeres and telomerase