title: Curcumin inhibits telomerase and induces telomere shortening and apoptosis in brain tumour cells.
abstract: Curcumin, a polyphenolic compound isolated from Curcuma longa (Turmeric) is widely used in traditional Ayurvedic medicine. Its potential therapeutic effects on a variety of diseases have long been known. Though anti-tumour effects of curcumin have been reported earlier, its mode of action and telomerase inhibitory effects are not clearly determined in brain tumour cells. In the present study, we demonstrate that curcumin binds to cell surface membrane and infiltrates into cytoplasm to initiate apoptotic events. Curcumin treatment has resulted in higher cytotoxicity in the cells that express telomerase enzyme, highlighting its potential as an anticancer agent. Curcumin induced growth inhibition and cell cycle arrest at G2/M phase in the glioblastoma and medulloblastoma cells used in the study. Gene and protein expression analyses revealed that curcumin down-regulated CCNE1, E2F1 and CDK2 and up-regulated the expression of PTEN genes resulting in growth arrest at G2/M phase. Curcumin-induced apoptosis is found to be associated with increased caspase-3/7 activity and overexpression of Bax. In addition, down-regulation of Bcl2 and survivin was observed in curcumin-treated cells. Besides these effects, we found curcumin to be inhibiting telomerase activity and down-regulating hTERT mRNA expression leading to telomere shortening. We conclude that telomerase inhibitory effects of curcumin underscore its use in adjuvant cancer therapy.
authors.affiliation: 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.forename: M Pradeepa
authors.initials: MP
authors.lastname: Hande
authors.forename: Guruprasad
authors.initials: G
authors.lastname: Kalthur
authors.forename: M Prakash
authors.initials: MP
authors.lastname: Hande
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D003474:Curcumin / Q000378:metabolism / Q000494:pharmacology*; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D059506:Telomere Shortening / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C475820:CCNE1 protein, human; D019927:Cyclin E; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D015513:Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C509186:TERT protein, human; D019098:Telomerase; D003474:Curcumin