TY - JOUR
T1 - Curcumin suppresses growth and induces apoptosis in primary effusion lymphoma
AU - Uddin, Shahab
AU - Hussain, Azhar R.
AU - Manogaran, Pulicat S.
AU - Al-Hussein, Khaled
AU - Platanias, Leonidas C.
AU - Gutierrez, Marina I.
AU - Bhatia, Kishor G.
PY - 2005/10/27
Y1 - 2005/10/27
N2 - The mechanisms that regulate induction of the antiapoptotic state and mitogenic signals in primary effusion lymphoma (PEL) are not well known. In efforts to identify novel approaches to block the proliferation of PEL cells, we found that curcumin (diferuloylmethane), a natural compound isolated from the plant Curcuma Ionga, inhibits cell proliferation and induces apoptosis in a dose dependent manner in several PEL cell lines. Such effects of curcumin appear to result from suppression of the constitutively active STAT3 through inhibition of Janus kinase 1 (JAK1). Our data also demonstrate that curcumin induces loss of mitochondrial membrane potential with subsequent release of cytochrome c and activation of caspase-3, followed by polyadenosin-5′-diphosphate-ribose polymerase (PARP) cleavage. Altogether, our findings suggest a novel function for curcumin, acting as a suppressor of JAK-1 and STAT3 activation in PEL cells, leading to inhibition of proliferation and induction of caspase-dependent apoptosis. Therefore, curcumin may have a future therapeutic role in PEL and possibly other malignancies with constitutive activation of STAT3.
AB - The mechanisms that regulate induction of the antiapoptotic state and mitogenic signals in primary effusion lymphoma (PEL) are not well known. In efforts to identify novel approaches to block the proliferation of PEL cells, we found that curcumin (diferuloylmethane), a natural compound isolated from the plant Curcuma Ionga, inhibits cell proliferation and induces apoptosis in a dose dependent manner in several PEL cell lines. Such effects of curcumin appear to result from suppression of the constitutively active STAT3 through inhibition of Janus kinase 1 (JAK1). Our data also demonstrate that curcumin induces loss of mitochondrial membrane potential with subsequent release of cytochrome c and activation of caspase-3, followed by polyadenosin-5′-diphosphate-ribose polymerase (PARP) cleavage. Altogether, our findings suggest a novel function for curcumin, acting as a suppressor of JAK-1 and STAT3 activation in PEL cells, leading to inhibition of proliferation and induction of caspase-dependent apoptosis. Therefore, curcumin may have a future therapeutic role in PEL and possibly other malignancies with constitutive activation of STAT3.
KW - Cell death
KW - Curcumin
KW - NHL therapy
KW - PEL
UR - http://www.scopus.com/inward/record.url?scp=27644477618&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27644477618&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1208864
DO - 10.1038/sj.onc.1208864
M3 - Article
C2 - 16044161
AN - SCOPUS:27644477618
SN - 0950-9232
VL - 24
SP - 7022
EP - 7030
JO - Oncogene
JF - Oncogene
IS - 47
ER -