LLL12B, a small molecule STAT3 inhibitor, induces growth arrest, apoptosis, and enhances cisplatin-mediated cytotoxicity in medulloblastoma cells
MetadataShow full item record
AbstractSignal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor and an oncogene product, which plays a pivotal role in tumor progression. Therefore, targeting persistent STAT3 signaling directly is an attractive anticancer strategy. The aim of this study is to test the efficacy of a novel STAT3 small molecule inhibitor, LLL12B, in suppressing medulloblastoma cells in vitro and tumor growth in vivo. LLL12B selectively inhibited the induction of STAT3 phosphorylation by interleukin-6 but not induction of STAT1 phosphorylation by INF-γ. LLL12B also induced apoptosis in human medulloblastoma cells. In addition, LLL12B exhibited good oral bioavailability in vivo and potent suppressive activity in tumor growth of medulloblastoma cells in vivo. Besides, combining LLL12B with cisplatin showed greater inhibition of cell viability and tumorsphere formation as well as induction of apoptosis comparing to single agent treatment in medulloblastoma cells. Furthermore, LLL12B and cisplatin combination exhibited greater suppression of medulloblastoma tumor growth than monotherapy in vivo. The present study supported that LLL12B is a novel therapeutic agent for medulloblastoma and the combination of LLL12B with a chemotherapeutic agent cisplatin may be an effective approach for medulloblastoma therapy. Copyright 2021, The Author(s).
SponsorsThis research was supported by the NIH/NINDS 1R01NS087213-01A1 Grant.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/15177
- A novel small molecule LLL12B inhibits STAT3 signaling and sensitizes ovarian cancer cell to paclitaxel and cisplatin.
- Authors: Zhang R, Yang X, Roque DM, Li C, Lin J
- Issue date: 2021
- A novel small molecular STAT3 inhibitor, LY5, inhibits cell viability, cell migration, and angiogenesis in medulloblastoma cells.
- Authors: Xiao H, Bid HK, Jou D, Wu X, Yu W, Li C, Houghton PJ, Lin J
- Issue date: 2015 Feb 6
- Targeting Upstream Kinases of STAT3 in Human Medulloblastoma Cells.
- Authors: Wei J, Ma L, Li C, Pierson CR, Finlay JL, Lin J
- Issue date: 2019
- The small molecule, LLL12, inhibits STAT3 phosphorylation and induces apoptosis in medulloblastoma and glioblastoma cells.
- Authors: Ball S, Li C, Li PK, Lin J
- Issue date: 2011 Apr 19
- LLY17, a novel small molecule STAT3 inhibitor induces apoptosis and suppresses cell migration and tumor growth in triple-negative breast cancer.
- Authors: Pan L, Chen X, Fu S, Yu W, Li C, Wang T, Lo HW, Lin J
- Issue date: 2020 May