Oxymatrine attenuates tumor growth and deactivates STAT5 signaling in a lung cancer xenograft model
Jung, Y.Y Shanmugam, M.K Narula, A.S Kim, C Lee, J.H Namjoshi, O.A Blough, B.E Sethi, G Ahn, K.S
Jung, Y.Y
Narula, A.S
Kim, C
Lee, J.H
Namjoshi, O.A
Blough, B.E
Ahn, K.S
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Alternative Title
Abstract
Oxymatrine (OMT) is a major alkaloid found in radix Sophorae flavescentis extract and has been reported to exhibit various pharmacological activities. We elucidated the detailed molecular mechanism(s) underlying the therapeutic actions of OMT in non-small cell lung cancer (NSCLC) cells and a xenograft mouse model. Because the STAT5 signaling cascade has a significant role in regulating cell proliferation and survival in tumor cells, we hypothesized that OMT may disrupt this signaling cascade to exert its anticancer effects. We found that OMT can inhibit the constitutive activation of STAT5 by suppressing the activation of JAK1/2 and c-Src, nuclear localization, as well as STAT5 binding to DNA in A549 cells and abrogated IL-6-induced STAT5 phosphorylation in H1299 cells. We also report that a sub-optimal concentration of OMT when used in combination with a low dose of paclitaxel produced significant anti-cancer effects by inhibiting cell proliferation and causing substantial apoptosis. In a preclinical lung cancer mouse model, OMT when used in combination with paclitaxel produced a significant reduction in tumor volume. These results suggest that OMT in combination with paclitaxel can cause an attenuation of lung cancer growth both in vitro and in vivo. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords
DNA, interleukin 6, Janus kinase 1, Janus kinase 2, matrine, oxymatrine, paclitaxel, protein tyrosine kinase, STAT5 protein, A-549 cell line, animal experiment, animal model, animal tissue, antineoplastic activity, antiproliferative activity, apoptosis, Article, cancer inhibition, cancer size, cancer survival, cell nucleus, cell proliferation, concentration response, controlled study, drug cytotoxicity, drug efficacy, drug mechanism, drug potentiation, drug structure, enzyme inhibition, female, G1 phase cell cycle checkpoint, human, human cell, in vitro study, in vivo study, mouse, mouse model, NCI-H1299 cell line, non small cell lung cancer, nonhuman, protein analysis, protein DNA binding, protein induction, protein localization, protein phosphorylation, signal transduction, tumor xenograft
Source Title
Cancers
Publisher
Series/Report No.
Collections
Rights
Attribution 4.0 International
Date
2019
DOI
10.3390/cancers11010049
Type
Article