journal article·2021-10-26Open access

Apoptotic Effect of Brassinin via Inhibition of CNOT2 and Activation of p53 and Its Combination Effect with Doxorubicin

Woon Yi Park, Ji Eon Park, Ji Hoon Jung

Applied Sciences· Volume 11· Issue 21

Abstract

Brassinin derived from Chinese cabbage has been reported to act as an anti-cancer agent on prostate, liver, and colon cancer cells. However, its mechanism and impact are largely unknown in colon cancer cells. Here, we first published a report that Brassinin induces apoptosis and inhibits the survival of colon cancer cells by activating p53. We found that Brassinin induces p53 and p21 dose- and time-dependent manner in wild type of p53 colon cancer cells. Interestingly, Brassinin induces apoptosis in wild-type of p53 cancer cells, but not in null-type of p53 cancer cells dose dependently. Additionally, Brassinin induces apoptosis through L5. Furthermore, Brassinin enhanced the apoptotic effect with doxorubicin by activating p53. Altogether, our findings suggest that Brassinin is a new p53 regulator via induce apoptosis and inhibit the proliferation in colon cancer cells.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Cancer-related Molecular Pathways · Cancer, Lipids, and Metabolism · RNA Research and Splicing

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea

Funding

National Research Foundation of Korea

References (34)

Show source-provided references
1. RNA-binding motif protein 10 induces apoptosis and suppresses proliferation by activating p5310.1038/s41388-019-1034-9 ↗
2. Live or let die: The cell’s response to p5310.1038/nrc864 ↗
3. Jung, J.H., Lee, H., Zeng, S.X., and Lu, H. (2020). RBM10, a New Regulator of p53. Cells, 9.10.3390/cells9092107 ↗
4. Pleckstrin homology domain-containing protein PHLDB3 supports cancer growth via a negative feedback loop involving p5310.1038/ncomms13755 ↗
5. Cooperation between the ribosomal proteins L5 and L11 in the p53 pathway10.1038/onc.2008.189 ↗
6. Lee, J., Jung, J.H., Hwang, J., Park, J.E., Kim, J.H., Park, W.Y., Suh, J.Y., and Kim, S.H. (2019). CNOT2 Is Critically Involved in Atorvastatin Induced Apoptotic and Autophagic Cell Death in Non-Small Cell Lung Cancers. Cancers, 11.10.3390/cancers11101470 ↗
7. Perturbation of 60 S ribosomal biogenesis results in ribosomal protein L5- and L11-dependent p53 activation10.1074/jbc.M109.098442 ↗
8. Hao, Q., Chen, Y., and Zhou, X. (2020). The Janus Face of p53-Targeting Ubiquitin Ligases. Cells, 9.10.3390/cells9071656 ↗
9. Regulation of the MDM2-p53 pathway by ribosomal protein L11 involves a post-ubiquitination mechanism10.1074/jbc.M602596200 ↗
10. Ribosomal proteins L11 and L5 activate TAp73 by overcoming MDM2 inhibition10.1038/cdd.2014.167 ↗
11. Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L510.1074/jbc.M403722200 ↗
12. Ribosomal protein L23 activates p53 by inhibiting MDM2 function in response to ribosomal perturbation but not to translation inhibition10.1128/MCB.24.17.7654-7668.2004 ↗
13. Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors
14. Colorectal cancer statistics, 202010.3322/caac.21601 ↗
15. Polk, A., Vistisen, K., Vaage-Nilsen, M., and Nielsen, D.L. (2014). A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity. BMC Pharm. Toxicol, 15.10.1186/2050-6511-15-47 ↗
16. Efficacy and side effect of continuous intra-arterial infusion of high-dose 5-FU for liver metastases of colorectal cancer
17. Oxaliplatin-induced ototoxicity in adjuvant setting for colorectal cancer: Unusual side effect10.1007/s12029-013-9489-3 ↗
18. Hong, T., Ham, J., Song, J., Song, G., and Lim, W. (2021). Brassinin Inhibits Proliferation in Human Liver Cancer Cells via Mitochondrial Dysfunction. Cells, 10.10.3390/cells10020332 ↗
19. Brassinin enhances the anticancer actions of paclitaxel by targeting multiple signaling pathways in colorectal cancer cells10.1002/ptr.7095 ↗
20. Yang, M.H., Lee, J.H., Ko, J.H., Jung, S.H., Sethi, G., and Ahn, K.S. (2019). Brassinin Represses Invasive Potential of Lung Carcinoma Cells through Deactivation of PI3K/Akt/mTOR Signaling Cascade. Molecules, 24.10.3390/molecules24081584 ↗
21. Farnesiferol c induces apoptosis via regulation of L11 and c-Myc with combinational potential with anticancer drugs in non-small-cell lung cancers10.1038/srep26844 ↗
22. Jung, J.H., Lee, H., Kim, J.H., Sim, D.Y., Ahn, H., Kim, B., Chang, S., and Kim, S.H. (2019). p53-Dependent Apoptotic Effect of Puromycin via Binding of Ribosomal Protein L5 and L11 to MDM2 and its Combination Effect with RITA or Doxorubicin. Cancers, 11.10.3390/cancers11040582 ↗
23. RP-MDM2-p53 Pathway: Linking Ribosomal Biogenesis and Tumor Surveillance10.1016/j.trecan.2016.03.002 ↗
24. Splicing-factor oncoprotein SRSF1 stabilizes p53 via RPL5 and induces cellular senescence10.1016/j.molcel.2013.02.001 ↗
25. Hydrophilic residues are crucial for ribosomal protein L11 (RPL11) interaction with zinc finger domain of MDM2 and p53 protein activation10.1074/jbc.M111.277012 ↗
26. GRWD1 negatively regulates p53 via the RPL11-MDM2 pathway and promotes tumorigenesis10.15252/embr.201642444 ↗
27. Structure of human MDM2 complexed with RPL11 reveals the molecular basis of p53 activation10.1101/gad.261792.115 ↗
28. The role of haploinsufficiency of RPS14 and p53 activation in the molecular pathogenesis of the 5q- syndrome10.4081/pr.2011.s2.e10 ↗
29. Inauhzin sensitizes p53-dependent cytotoxicity and tumor suppression of chemotherapeutic agents10.1593/neo.13142 ↗
30. A small molecule Inauhzin inhibits SIRT1 activity and suppresses tumour growth through activation of p5310.1002/emmm.201100211 ↗
31. Nerve growth factor receptor negates the tumor suppressor p53 as a feedback regulator10.7554/eLife.15099 ↗
32. Non-genotoxic activation of p53 through the RPL11-dependent ribosomal stress pathway10.1093/carcin/bgu220 ↗
33. CNOT2 promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231 breast cancer cells10.1016/j.canlet.2017.09.052 ↗
34. Jung, J.H., Lee, H.J., Kim, J.H., Sim, D.Y., Im, E., Kim, S., Chang, S., and Kim, S.H. (2020). Colocalization of MID1IP1 and c-Myc is Critically Involved in Liver Cancer Growth via Regulation of Ribosomal Protein L5 and L11 and CNOT2. Cells, 9.10.3390/cells9040985 ↗