Nam, Dongwoo Song, Junho Kim, Sung-Moo Chiang, Shu Yuan Kim, Ji-Sung Chung, Won-Seok Jang, Hyeung-Jin Jung, Sang Hoon Na, Young-Soon Kim, Sung-Hoon Shim, Bum Sang Ahn, Kwang Seok 2024-01-20T10:30:14Z 2024-01-20T10:30:14Z 2021-09-05 2014-03 1096-620X https://pubs.kist.re.kr/handle/201004/127047 The identification of the active compounds of herbal medicines and the molecular targets of those compounds is an attractive therapeutic objective. Reynoutria elliptica has been used for the treatment of various inflammatory diseases as a Korean folk remedy. Based on the evidence that anti-inflammatory agents frequently exert antiproliferative activity, we tested two sesquiterpene derivatives, 8-hydrocalamenene (HC) and 8,14-dihydrocalamenene (DHC), for their ability to induce apoptosis and suppress signal transducer and activator of transcription 3 (STAT3) activation in multiple myeloma (MM) U266 cells. We found that HC inhibited cell viability in U266, but not in peripheral blood mononuclear cells. HC exerted significant cytotoxicity and induced substantial subG1-phase arrest and apoptosis as compared with DHC. HC inhibited the expression of gene products involved in antiapoptosis (Bcl-2 and Bcl-xL), proliferation (cyclin D1), and invasion (MMP-9), all of which are known to be regulated by STAT3. Furthermore, HC up-regulated cyclin-dependent kinase inhibitor p21 and induced apoptosis through the activation of caspase-8, -9, and -3 in U266 cells. Interestingly, HC blocked constitutive STAT3 activation through the inhibition of activation of upstream kinases Janus-like kinase 1 (JAK1), JAK2, and c-Src and up-regulated PIAS3. Deletion of STAT3 reversed cytotoxic effects and the down-regulation of cyclin D1 and c-myc by HC in MM cells. Finally, this sesquiterpene significantly synergized the cytotoxic and apoptotic effects of bortezomib in U266 cells. Taken together, these results suggest that HC is a novel blocker of STAT3 activation which may have a potential in the prevention and treatment of MM. English MARY ANN LIEBERT, INC NITRIC-OXIDE SYNTHASE SIGNAL TRANSDUCERS CANCER GENE PHOSPHORYLATION INFLAMMATION APOPTOSIS TUMORS 8-Hydrocalamenene, Derived from Reynoutria elliptica, Suppresses Constitutive STAT3 Activation, Inhibiting Proliferation and Enhancing Chemosensitization of Human Multiple Myeloma Cells Article 10.1089/jmf.2012.2628 1 JOURNAL OF MEDICINAL FOOD, v.17, no.3, pp.365 - 373 JOURNAL OF MEDICINAL FOOD 17 3 365 373 scie scopus kci ART001860855 000336216800010 2-s2.0-84896959908 Chemistry, Medicinal Food Science & Technology Nutrition & Dietetics Pharmacology & Pharmacy Food Science & Technology Nutrition & Dietetics Article NITRIC-OXIDE SYNTHASE SIGNAL TRANSDUCERS CANCER GENE PHOSPHORYLATION INFLAMMATION APOPTOSIS TUMORS apoptosis chemosensitization 8-hydrocalamenene Reynoutria elliptica STAT3