Isoliquiritigenin inhibits the growth of multiple myeloma via blocking IL-6 signaling.
Previous studies have suggested that isoliquiritigenin (ISL) has anti-carcinogenic activity in several kinds of solid tumors, however, little is known about the effects of ISL on hematologic malignancies. In this study, we investigated the effects of ISL on multiple myeloma (MM) cells both in vitro and in vivo. The results showed that ISL could inhibit the growth of MM cells and induce their apoptosis in time- and dose-dependent manners. ISL exhibited significant anti-tumor activity in MM xenograft models and synergistically enhanced the anti-myeloma activity of adriamycin. Further analysis demonstrated that ISL not only downregulated IL-6 expression but also significantly decreased levels of phosphorylated ERK and STAT3 and could inhibit phosphorylation levels of ERK and STAT3 induced by recombinant human IL-6, which are critical signaling proteins in IL-6 signaling regulation networks. Taken together, our findings suggested that ISL could inhibit the growth of MM via blocking IL-6 signaling and might serve as a promising therapeutic agent for treatment of MM.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, No.1, Keyuan Road 4, Gaopeng Street, Chengdu, 610041 Sichuan, China.
Xiangzheng
X
Chen
Yangping
Y
Wu
Yangfu
Y
Jiang
Yan
Y
Zhou
Yuxi
Y
Wang
Yuqin
Y
Yao
Cheng
C
Yi
Lantu
L
Gou
Jinliang
J
Yang
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002470:Cell Survival; D047188:Chalcones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020287:In Situ Nick-End Labeling; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
D016588:Anticarcinogenic Agents; D047188:Chalcones; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D004317:Doxorubicin; C040920:isoliquiritigenin