Blockage of the JAK/STAT3 signaling pathway in multiple myeloma by leelamine.

Abstract

BACKGROUND:

Leelamine (LEE) is a lipophilic diterpene amine phytochemical, which can be naturally extracted from pine's bark trees. It has been extensively studied recently for its promising chemopreventive and anti-cancer effects against various cancers such as that of prostate and breast.

HYPOTHESIS:

We examined the potential impact of LEE in affecting the activation of signal transducer and activator of transcription 3 (STAT3) and promoting apoptosis in human multiple myeloma (MM) cells.

METHODS:

We evaluated the effect of LEE on STAT3 signaling pathway in MM cells by using Western blot analysis and reverse transcription polymerase chain reaction (RT-PCR). Thereafter, apoptosis was evaluated using cell cycle analysis and Annexin V assay.

RESULTS:

We noted that LEE could attenuate the phosphorylation of STAT3 and other up-stream signaling molecules such as JAK1, JAK2, and Src activation in U266 and MM.1S cells. It also diminished STAT3 translocation into the nucleus and enhanced the expression of protein-tyrosine phosphatase epsilon (PTPε). Additionally, LEE caused cell cycle arrest and synergistically augmented the apoptotic actions of bortezomib against MM cells.

CONCLUSIONS:

Our data indicates that LEE could block STAT3 signaling cascade linked to tumorigenesis and can be used in combination with approved anti-cancer agents in attenuating MM growth and survival.

• Authors: Young Yun Jung, Jae-Young Um, Omaima Nasif, Sulaiman Ali Alharbi, Gautam Sethi, Kwang Seok Ahn
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 87 Pg. 153574 (Jul 2021) ISSN: 1618-095X [Electronic] Germany
• PMID: 34006448 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier GmbH. All rights reserved.

Chemical References

• Abietanes
• Antineoplastic Agents
• STAT3 Transcription Factor
• STAT3 protein, human
• dehydroabietylamine
• JAK1 protein, human
• JAK2 protein, human
• Janus Kinase 1
• Janus Kinase 2

Topics

• Abietanes (pharmacology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Gene Expression Regulation (drug effects)
• Humans
• Janus Kinase 1 (genetics, metabolism)
• Janus Kinase 2 (genetics, metabolism)
• Multiple Myeloma (drug therapy, metabolism)
• Phosphorylation (drug effects)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)