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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Safa, Majid Tavasoli, Behnaz Manafi, Rima Kiani, Fatemeh Kashiri, Meysam Ebrahimi, Saber Kazemi, Ahmad |
| Description | Author Affiliation: Safa M ( Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran, safa.m@iums.ac.ir.) |
| Abstract | B cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common type of cancer in children. Dramatic improvements in primary therapy for childhood ALL have led to an overall cure rate of 80 %, providing opportunities for innovative combined-modality strategies that would increase cure rates while reducing the toxic side effects of current intensive regimens. In this study, we report that indole-3-carbinol (I3C), a natural phytochemical found in cruciferous vegetables, had anti-leukemic properties in BCP-ALL NALM-6 cells. I3C induced cell growth inhibition by G1 cell cycle arrest and triggered apoptosis in a dose- and time-dependent manner. p53, p21, and Bax proteins showed increased expression after I3C treatment. Real-time PCR analysis of pro-apoptotic p53 target genes revealed up-regulation of PUMA, NOXA, and Apaf-1. I3C also suppressed constitutive nuclear factor-κB (NF-κB) activation and inhibited the protein expression of NF-kappa B-regulated antiapoptotic (IAP1, Bcl-xL, Bcl-2, XIAP) and proliferative (c-Myc) gene products. Coadministration of I3C with the topoisomerase II inhibitor, doxorubicin, potentiates cytotoxic effects compared with either agent alone. Apoptosis induction by the drug combination was associated with enhanced caspase-9 activation and PARP cleavage. Furthermore, I3C abolished doxorubicin-induced NF-κB activity as evidenced by decreased nuclear accumulation of p65, inhibition of IκB phosphorylation and its degradation, and decreased NF-κB DNA-binding activity. Western blot analysis revealed that doxorubicin-induced Bcl-2 protein expression was inhibited by I3C. Overall, our results indicated that using nontoxic agents, such as I3C, in combination with anthracyclines might provide a new insight into the development of novel combination therapies in childhood BCP-ALL. |
| File Format | HTM / HTML |
| ISSN | 10104283 |
| Issue Number | 5 |
| Volume Number | 36 |
| e-ISSN | 14230380 |
| Journal | Tumor Biology |
| Language | English |
| Publisher | Springer |
| Publisher Date | 2015-05-01 |
| Publisher Place | Netherlands |
| Access Restriction | Subscribed |
| Subject Keyword | Discipline Medicine__semicolon__oncology Indoles Administration & Dosage Nf-kappa B Genetics Precursor Cell Lymphoblastic Leukemia-lymphoma Drug Therapy Tumor Suppressor Protein P53 Apoptosis Drug Effects B-lymphocytes Pathology Cell Line, Tumor Gene Expression Regulation, Neoplastic Humans Neoplasm Proteins Biosynthesis Phosphorylation Signal Transduction Tumor Necrosis Factor-alpha Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Cancer Research |
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