TY - JOUR
T1 - Piperlongumine inhibits LMP1/MYC-dependent mouse B-lymphoma cells
AU - Han, Seong Su
AU - Tompkins, Van S.
AU - Son, Dong Ju
AU - Kamberos, Natalie L.
AU - Stunz, Laura L.
AU - Halwani, Ahmad
AU - Bishop, Gail A.
AU - Janz, Siegfried
N1 - Funding Information:
We thank Dr. Thomas Raife, University of Iowa DeGowin Blood Center, for the kind provision of leukoreduction chambers for preparation of peripheral blood B-lymphocytes. This work was funded by research grants from the NCI ( R01CA151354 ; S.J.) and NNSFC ( 81250110552 ; V.T.), as well as additional support by a Hyundai Hope on Wheels Research Scholar Grant (N.L.K.), Roy J. Carver Charitable Trust Collaborative Pilot Grant (G.A.B. and S.J.) and the Iowa City Veterans Affairs Medical Center (G.A.B.).
PY - 2013/7/12
Y1 - 2013/7/12
N2 - Piperlongumine (PL), isolated from the fruit of Long pepper, Piper longum, is a cancer-inhibiting compound that selectively kills tumor cells while sparing their normal counterparts. Here we evaluated the efficacy with which PL suppresses malignant B cells derived from a newly developed, double-transgenic mouse model of human endemic Burkitt lymphoma (BL), designated mCD40-LMP1/iMycEμ. PL inhibited tumor cell proliferation in a concentration-dependent manner and induced apoptosis of neoplastic but not normal B cells. Treatment with PL resulted in downregulation of EBV-encoded LMP1, cellular Myc, constitutive NF-κB activity, and a host of LMP1-Myc-NF-κB-regulated target genes including Aurka, Bcat1, Bub1b, Ccnb1, Chek1, Fancd2, Tfrc and Xrcc6. Of note, p21Cip1-encoding Cdkn1a was suppressed independent of changes in Trp53 mRNA levels and p53 DNA-binding activity. Considering the central role of the LMP1-NF-κB-Myc axis in B-lineage neoplasia, these findings further our understanding of the mechanisms by which PL inhibits B-lymphoma and provide a preclinical rationale for the inclusion of PL in new interventions in blood cancers.
AB - Piperlongumine (PL), isolated from the fruit of Long pepper, Piper longum, is a cancer-inhibiting compound that selectively kills tumor cells while sparing their normal counterparts. Here we evaluated the efficacy with which PL suppresses malignant B cells derived from a newly developed, double-transgenic mouse model of human endemic Burkitt lymphoma (BL), designated mCD40-LMP1/iMycEμ. PL inhibited tumor cell proliferation in a concentration-dependent manner and induced apoptosis of neoplastic but not normal B cells. Treatment with PL resulted in downregulation of EBV-encoded LMP1, cellular Myc, constitutive NF-κB activity, and a host of LMP1-Myc-NF-κB-regulated target genes including Aurka, Bcat1, Bub1b, Ccnb1, Chek1, Fancd2, Tfrc and Xrcc6. Of note, p21Cip1-encoding Cdkn1a was suppressed independent of changes in Trp53 mRNA levels and p53 DNA-binding activity. Considering the central role of the LMP1-NF-κB-Myc axis in B-lineage neoplasia, these findings further our understanding of the mechanisms by which PL inhibits B-lymphoma and provide a preclinical rationale for the inclusion of PL in new interventions in blood cancers.
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U2 - 10.1016/j.bbrc.2013.06.012
DO - 10.1016/j.bbrc.2013.06.012
M3 - Article
C2 - 23764397
AN - SCOPUS:84880040845
SN - 0006-291X
VL - 436
SP - 660
EP - 665
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -
