Plumbagin alters telomere dynamics, induces DNA damage and cell death in human brain tumour cells

Aik Kia Khaw, Safoura Sameni, Shriram Venkatesan, Guruprasad Kalthur, M. Prakash Hande

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)86-95
Number of pages10
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume793
DOIs
Publication statusPublished - 01-11-2015

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Telomere
Brain Neoplasms
DNA Damage
Cell Death
Telomerase
Proto-Oncogene Proteins c-bcl-2
Telomere Shortening
Cyclin B1
Caspase 7
Naphthoquinones
Neoplasms
Phytochemicals
Therapeutics
Cell Cycle Checkpoints
Palliative Care
Caspase 3
plumbagin
Up-Regulation
Down-Regulation
Apoptosis

All Science Journal Classification (ASJC) codes

  • Health, Toxicology and Mutagenesis
  • Genetics
  • Medicine(all)

Cite this

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Plumbagin alters telomere dynamics, induces DNA damage and cell death in human brain tumour cells. / Khaw, Aik Kia; Sameni, Safoura; Venkatesan, Shriram; Kalthur, Guruprasad; Hande, M. Prakash.

In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 793, 01.11.2015, p. 86-95.

Research output: Contribution to journalArticle

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