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Theobromine, the primary methylxanthine found in Theobroma cacao, inhibits malignant glioblastoma cell growth by negatively regulating Akt/mammalian target of rapamycin kinase (LB836)
Author(s) -
Sugimoto Naotoshi,
Miwa Shinji,
Katakura Masanori,
Matsuzaki Kentaro,
Shido Osamu,
Tsuchiya Hiroyuki,
Yachie Akihiro
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb836
Subject(s) - theobromine , caffeine , chemistry , theobroma , protein kinase b , theophylline , cell growth , kinase , cancer research , pharmacology , signal transduction , biochemistry , biology , medicine , botany
Theobromine, a caffeine derivative, is the primary methylxanthine produced by Theobroma cacao. We previously showed that methylxanthines, including caffeine and theophylline, have anti‐tumor and anti‐inflammatory effects, which are in part mediated by their inhibition of phosphodiesterase (PDE) [1‐3]. A member of the PDE family, PDE4, is widely expressed in and promotes the growth of glioblastoma, the most common type of brain tumor. Here, we investigate whether theobromine could exert growth inhibitory effects on U87‐MG, a cell line derived from human malignant glioma. We show that theobromine treatment elevates intracellular cAMP levels, indicating the prevention of PDE4 by theobromine, whereas it attenuates the Akt/mammalian target of rapamycin kinase pathway. Theobromine also inhibits cell growth. These results suggest that theobromine might be extremely effective in preventing human glioblastoma. [1] Miwa S, Sugimoto N et al. Int J Oncol., 2011; 39: 465‐472. [2] Miwa S, Sugimoto N et al. Anticancer Res., 2012; 32: 3643‐3649. [3] Saito T, Sugimoto N et al. ScientificWorldJournal, 2012; 2012:748572 (8pages).