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Mda‐7 / IL‐24 induces apoptosis of diverse cancer cell lines through JAK/STAT‐independent pathways
Author(s) -
Sauane Moira,
Gopalkrishnan Rahul V.,
Lebedeva Irina,
Mei Mei Xin,
Sarkar Devanand,
Su ZhaoZhong,
Kang DongChul,
Dent Paul,
Pestka Sidney,
Fisher Paul B.
Publication year - 2003
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10309
Subject(s) - stat , jak stat signaling pathway , apoptosis , cytokine , tyrosine kinase , biology , signal transduction , p38 mitogen activated protein kinases , cancer research , microbiology and biotechnology , mapk/erk pathway , cell culture , stat3 , immunology , biochemistry , genetics
Experimental evidence documents that the MDA‐7 / IL‐24 protein (an IL‐10 family cytokine) binds to IL‐20 and IL‐22 receptor complexes resulting in the activation of JAK/STAT signaling pathways. Recent published reports utilizing human blood derived primary lymphocytes have provided additional confirmatory evidence relating to the cytokine properties of this molecule. A notable attribute of mda‐7 / IL‐24 is its cancer cell‐specific apoptosis inducing capacity, which currently remains incompletely understood. Treatment with distinctive tyrosine kinase inhibitors (Genistein and AG18) or a JAK‐selective inhibitor (AG490) did not prevent Ad. mda‐7 induced apoptosis in diverse cell lines. In addition, there is no apparent correlation between patterns of expression of IL‐20R1, IL‐20R2, and IL‐22R mRNA and susceptibility to Ad .mda‐7 in different cell lines. Furthermore, Ad. mda‐7 is able to induce killing in STAT/JAK deficient cells. In contrast, treatment with the p38 MAPK selective inhibitor SB203580, partially inhibited apoptosis induced by Ad .mda‐7 in different cell lines. These results demonstrate for the first time that signaling events leading to susceptibility to Ad .mda‐7 induced apoptosis, might be tyrosine kinase independent and can thus be distinguished from its cytokine function related properties mediated by the IL‐20/IL‐22 receptor complexes that require JAK/STAT kinase activity. J. Cell. Physiol. 196: 334–345, 2003. © 2003 Wiley‐Liss, Inc.