Abstract:
:Recent studies indicate that gossypol possesses potent antitumor activities in vitro and in vivo. The nuclear factor-kappa B (NF-kappaB) plays an important role in tumor cell growth, proliferation, invasion, and survival. In this study, we investigated the effects and the molecular mechanisms of gossypol on NF-kappaB activation and NF-kappaB-related gene expression in human leukemia U937 cells. Treatment with concentrations of gossypol greater than 10 microM resulted in significant cell cytotoxicity and DNA fragmentation, indicative of apoptosis. Treatment with 10 microM gossypol also induced caspase-3 activation and poly(ADP-ribose)polymerase (PARP) cleavage, and resulted in the induction of apoptosis in approximately 20% of cells as determined by annexin-V staining 24h after treatment. Furthermore, gossypol exposure decreased the DNA-binding activity of NF-kappaB in a concentration-dependent manner. Treatment with gossypol also downregulated expression of NF-kappaB-regulated gene products, including inhibitor of apoptosis protein (IAP)-1, IAP-2, and X-linked IAP. Attenuation of NF-kappaB activity by pretreatment with PDTC, an NF-kappaB nuclear translocation inhibitor, significantly induced apoptosis in the presence of gossypol. Gossypol also suppressed NF-kappaB p65 mRNA accumulation, resulting in suppression of total NF-kappaB activity. This was associated with a downregulation of Sp1-binding activity, a transcription factor controlling p65 transcription. These results suggest that gossypol-induced apoptosis partially involves suppression of NF-kappaB activity.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Moon DO,Kim MO,Lee JD,Kim GYdoi
10.1016/j.canlet.2008.01.030subject
Has Abstractpub_date
2008-06-18 00:00:00pages
192-200issue
2eissn
0304-3835issn
1872-7980pii
S0304-3835(08)00050-5journal_volume
264pub_type
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