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Activation of nerve growth factor-induced B alpha by methylene-substituted diindolylmethanes in bladder cancer cells induces apoptosis and inhibits tumor growth.

ABSTRACT: Nerve growth factor-induced B (NGFI-B) genes are orphan nuclear receptors, and NGFI-B alpha (Nur77, TR3) is overexpressed in bladder tumors and bladder cancer cells compared with nontumorous bladder tissue. 1,1-Bis(3'-indolyl)-1-(p-methoxyphenyl)-methane (DIM-C-pPhOCH(3)) and 1,1-bis(3'-indolyl)-1-(p-phenyl)methane have previously been identified as activators of Nur77, and both compounds inhibited growth and induced apoptosis of UC-5 and KU7 bladder cancer cells. The proapoptotic effects of methylene-substituted diindolylmethanes (C-DIMs) were unaffected by cotreatment with leptomycin B and were dependent on nuclear Nur77, and RNA interference with a small inhibitory RNA for Nur77 (iNur77) demonstrated that C-DIM-induced activation of apoptosis was Nur77-dependent. Microarray analysis of DIM-C-pPhOCH(3)-induced genes in UC-5 bladder cancer cells showed that this compound induced multiple Nur77-dependent proapoptotic or growth inhibitory genes including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), cystathionase, p21, p8, and sestrin-2. DIM-C-pPhOCH(3) (25 mg/kg/d) also induced apoptosis and inhibited tumor growth in athymic nude mice bearing KU7 cells as xenografts, demonstrating that Nur77-active C-DIMs exhibit potential for bladder cancer chemotherapy by targeting Nur77, which is overexpressed in this tumor type.

SUBMITTER: Cho SD

PROVIDER: S-EPMC2835419 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Activation of nerve growth factor-induced B alpha by methylene-substituted diindolylmethanes in bladder cancer cells induces apoptosis and inhibits tumor growth.

Cho Sung Dae SD Lee Syng-Ook SO Chintharlapalli Sudhakar S Abdelrahim Maen M Khan Shaheen S Yoon Kyungsil K Kamat Ashish M AM Safe Stephen S

Molecular pharmacology 20091218 3

Nerve growth factor-induced B (NGFI-B) genes are orphan nuclear receptors, and NGFI-B alpha (Nur77, TR3) is overexpressed in bladder tumors and bladder cancer cells compared with nontumorous bladder tissue. 1,1-Bis(3'-indolyl)-1-(p-methoxyphenyl)-methane (DIM-C-pPhOCH(3)) and 1,1-bis(3'-indolyl)-1-(p-phenyl)methane have previously been identified as activators of Nur77, and both compounds inhibited growth and induced apoptosis of UC-5 and KU7 bladder cancer cells. The proapoptotic effects of met ...[more]

PMID: 20023005

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Activation of nerve growth factor-induced B alpha by methylene-substituted diindolylmethanes in bladder cancer cells induces apoptosis and inhibits tumor growth.

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Activation of nerve growth factor-induced B alpha by methylene-substituted diindolylmethanes in bladder cancer cells induces apoptosis and inhibits tumor growth.

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