Purpose/Objective:

NF-κB plays an essential role in cancer cell growth and metastasis by stimulating angiogenesis. Curcumin decreases the activity of several oncogenic transcriptional factors including NF-κB and HIF-1α, thus we investigated whether curcumin and its analogs EF-31 and UBS-109, could disrupt angiogenesis using colorectal cancer cells (CRC).

Methods:

HCT-116 and HT-29 cells were used in these experiments. HUVEC tube formation assay, Matrigel plug assay, Western blotting, and VEGF activity assay were carried out to determine the curcumin, EF-31 and UBS-109 role in angiogenesis. A subcutaneous xenograft mouse model was used to evaluate the in vivo effects of curcumin analogues.

Results:

Conditioned medium from HCT-116 or H-T29 cells exposed to curcumin, EF-31 and UBS-109 in vitro significantly blocked HUVEC tube assembly in comparison to control. In vivo, EF-31 and UBS-109 blocked the vascularization of subcutaneous matrigel plugs and the growth of CRC xenografts. We observed significant inhibition of VEGF synthesis and secretion in both colon cell lines treated with curcumin, EF-31 and UBS-109 in concert with the loss of HIF-1α expression, of which transcriptionally regulated by NF-κB. Similar effects were observed in tumors from animals treated with EF-31 and UBS-109. Further, EF-31 and UBS-109 treatment significantly decreased the tumor growth compared to untreated tumors. These results suggesting that curcumin, EF-31 and UBS-109 inhibits VEGF production in part through the degradation of HIF-1α and increased the cytoplasmic accumulation of NF-κB.

Conclusion:

Taken together, destabilization of HIF-1α and inhibition of NF-κB from cytoplasm to nuclear translocation may be important contributing factors to the antiangiogenic action of curcumin, EF-31 and UBS-109 in CRC.

Note: This abstract was not presented at the meeting.

Citation Format: Ganji Purnachandra Nagaraju, Mamoru Shoji, Bassel El Rayes. Targeting NF-κB by the curcumin and its analogs EF-31 and UBS-109 decreases growth and angiogenesis of colon cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4166. doi:10.1158/1538-7445.AM2015-4166