Z. Shi, N. An and S. Zhao contributed equally to this work.
In silico analysis of molecular mechanisms of legume lectin-induced apoptosis in cancer cells
Article first published online: 7 JAN 2013
© 2013 Blackwell Publishing Ltd
Volume 46, Issue 1, pages 86–96, February 2013
How to Cite
Shi, Z., An, N., Zhao, S., Li, X., Bao, J. K. and Yue, B. S. (2013), In silico analysis of molecular mechanisms of legume lectin-induced apoptosis in cancer cells. Cell Proliferation, 46: 86–96. doi: 10.1111/cpr.12009
- Issue published online: 7 JAN 2013
- Article first published online: 7 JAN 2013
- Manuscript Accepted: 20 OCT 2012
- Manuscript Received: 6 JUN 2012
- National Natural Science Foundation of China. Grant Numbers: 30970643, 81173093, J1103518
The legume lectin family, one of the most extensively studied plant lectin families, has received increasing attention for the remarkable anti-tumor activities of its members for binding specific cancer cell surface glycoconjugates. MicroRNAs, a class of small, non-coding RNAs, control translation and stability of mRNAs at post-transcriptional and translational levels. To date, accumulating evidence has revealed that microRNAs are involved in progression of a number of human diseases, especially cancers. However, the molecular manners of microRNA-modulated apoptosis in legume lectin-treated cancer cells are still under investigation.
Materials and methods
We performed in silico analyses to study the interactions between three typical legume lectins (ConA, SFL and SAL) and some specific sugar-containing receptors (for example, EGFR, TNFR1, HSP70 and HSP90). Additionally, we predicted some relevant microRNAs which could significantly regulate these aforementioned targetreceptors and thus inhibiting down-stream cancer-related signaling pathways.
The results showed that these three legume lectins could competitively bind sugar-containing receptors such as EGFR, TNFR1, HSP70 and HSP90 in two ways, via anti-apoptotic or survival pathways. On the one hand, the legume lectins could induce cancer cell death through triggering receptor-mediated signaling pathways, which resulted from indirect binding between legume lectins and mannoses resided in receptors. On the other hand, direct binding between legume lectins and receptors could lead to steric hindrance, which would disturb efficient interactions between them, and thus, the legume lectins would induce cancer cell death by triggering receptor-mediated signaling pathways. In addition, we identified several relevant microRNAs that regulated these targeted receptors, thereby ultimately causing cancer cell apoptosis.
These findings provide new perspectives for exploring microRNA-modulated cell death in legume lectin-treated cancer cells, which could be utilized in combination therapy for future cancer drug development.