RIPROXIMIN SUPPRESSES NF-ΚB AND ENGAGES THE FAS/CD95 RECEPTOR LEADING TO APOPTOSIS IN MDA-MB-231 AND SW-707 CANCER CELLS
| Main Author: | Joshua M. Mutiso1,2, Rania B. Georges3, Micah N.Sagini4 & Martin R. Berger*5 |
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| Format: | Article |
| Terbitan: |
, 2019
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| Subjects: | |
| Online Access: |
https://zenodo.org/record/2562831 |
Daftar Isi:
- Riproximin (Rpx), a type II ribosome-inactivating protein has high specificity for cancer glycans. The present study investigates the capacity of Rpx to engage the CD 95/FAS death receptor in human breast (MDA-MB-231) and colorectal (SW-707) cancer cells lines. To investigate the effect on apoptotic genes whenexposingMDA-MB-231 cells to Rpxat IC50concentration,a cDNA microarray was performed. Interestingly, Rpxtreatment caused a significant reduction (p≤ 0.05) of IKBKB, NIK, BCL2 and ROCK1mRNAexpression,whereas a significant upregulation of BAX, CASP3, CASP9, BID and ACIN1mRNA expression was induced. At protein level, a significant reduction of NF-κB in both treated cell lines was observed. Additionally, anti-apoptotic proteins were either not affected or were significantly reduced whereas pro-apoptotic proteins showed significantly increased expression. Of importance, Rpx was found to directly bind to the FAS death receptor activating both, the extrinsic and intrinsic apoptosis pathways through engagement of the FAS Associated Death Domain (FADD) and subsequent activation of the caspase cascade. These findings indicate that Rpx suppresses cancer cell proliferation and survival by inactivating NF-κB and ligating FAS to cause apoptosis in both cancer cell lines and point to the potential application of this lectin as a targeted anti-tumor agent.