Genistein induces growth arrest and suppresses telomerase activity in brain tumor cells.
Genistein, a soy isoflavone, has been reported to exhibit multiple effects, such as inducing cell cycle arrest, triggering apoptosis, inhibiting the activation of NF(K) B and inactivating several signaling cascades in human cancer cells. In vivo studies demonstrating antiangiogenesis and antimetastatic effects of genistein have also been reported. Here, we demonstrate that genistein inhibits the growth of glioblastoma multiforme and medulloblastoma cells with different TP53 mutations and radio-responses by arresting the cells at G2/M phase of the cell cycle. The cell cycle arrest was found to be independent of DNA damage and such an arrest was sustainable for at least 10 days even after drug removal. Annexin V staining revealed absence of apoptotic or necrotic cell populations after genistein treatment. This supports the observation that genistein induces insignificant DNA damage and indicates that the cell cycle arrest triggered does not lead to cell death. Gene and protein expression studies reveal similar changes in the same pathways following treatment in the cell types tested. Genistein was also able to inhibit telomerase activity resulting in telomere shortening. Thus, we demonstrate, for the first time, that genistein induces growth arrest in association with telomerase inhibition in brain tumor cells via the suppression of TR- and TERT mRNA. By elucidating the mechanisms of anticancer effects after genistein treatment in brain tumor cells, there will be a premise for the incorporation of genistein dietary sources to complement radiotherapy in brain tumor patients.
Department of Physiology, Genome Stability Laboratory, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Republic of Singapore.
Aik Kia
AK
Khaw
Jacklyn Wei Yan
JW
Yong
Guruprasad
G
Kalthur
M Prakash
MP
Hande
D017304:Annexin A5; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D004249:DNA Damage; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D019833:Genistein / Q000494:pharmacology*; D005909:Glioblastoma / Q000188:drug therapy; D006801:Humans; D008527:Medulloblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D012333:RNA, Messenger / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D059010:Single-Cell Analysis; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000187:drug effects / Q000235:genetics; D059506:Telomere Shortening / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D014407:Tumor Cells, Cultured
D017304:Annexin A5; D016588:Anticarcinogenic Agents; D012333:RNA, Messenger; D019833:Genistein; C509186:TERT protein, human; D019098:Telomerase