Cyproheptadine-induced myeloma cell apoptosis is associated with inhibition of the PI3K/AKT signaling.

Abstract

Recent studies revealed that the anti-allergic cyproheptadine displays anti-blood cancer activity. However, its mechanism is still elusive. In this study, cyproheptadine was found to decrease the expression of anti-apoptotic proteins, including Bcl-2, Mcl-1, and XIAP. More importantly, cyproheptadine-induced apoptosis was accompanied by suppressing AKT activation in myeloma cells. In the subsequent study, cyproheptadine was found to inhibit insulin-like growth factor 1-triggered AKT activation in a time- and concentration-dependent manner. Specifically, cyproheptadine blocked AKT translocation from nuclei for phosphorylation. This inhibition led to suppressed activation of p70S6K and 4EBP1, two key downstream signaling proteins in the PI3K/AKT pathway. However, cyproheptadine did not display inhibition on activation of IGF-1R or STAT3, possible upstream signals of AKT activation. These results further demonstrated that cyproheptadine suppresses the PI3K/AKT signaling pathway, which is probably critical for cyproheptadine-induced MM cell apoptosis.

• Authors: Jie Li, Biyin Cao, Shunye Zhou, Jingyu Zhu, Zubin Zhang, Tingjun Hou, Xinliang Mao
• Journal: European journal of haematology (Eur J Haematol) Vol. 91 Issue 6 Pg. 514-21 (Dec 2013) ISSN: 1600-0609 [Electronic] England
• PMID: 24033664 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Adaptor Proteins, Signal Transducing
• Cell Cycle Proteins
• EIF4EBP1 protein, human
• Phosphoproteins
• Cyproheptadine
• Proto-Oncogene Proteins c-akt
• Ribosomal Protein S6 Kinases, 70-kDa

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Apoptosis (drug effects)
• Cell Cycle Proteins
• Cell Line, Tumor
• Cyproheptadine (pharmacology)
• Humans
• Multiple Myeloma (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoproteins (metabolism)
• Phosphorylation (drug effects)
• Protein Transport (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Ribosomal Protein S6 Kinases, 70-kDa (metabolism)
• Signal Transduction (drug effects)