Journal
CELL BIOLOGY AND TOXICOLOGY
Volume 37, Issue 1, Pages 97-111Publisher
SPRINGER
DOI: 10.1007/s10565-020-09565-x
Keywords
CPUC002; Multiple myeloma; Apoptosis; p53; STAT3
Categories
Funding
- National Natural Science Foundation of China [81903625, 81903626, 81573278, 81872899, 81830105, 81673461]
- National Science & Technology Major Project [2017ZX09301014, 2018ZX09711001-005-023, 2018ZX09711001-003-007]
- Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University [SKLNMZZCX201823]
- Social Development Project of Jiangsu Provincial Science and Technology Department [BE2018711]
- Natural Science Foundation of Jiangsu Province [BK20180576]
- Double First-Class University project [CPU2018GF11, CPU2018GY17, CPU2018GF05]
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CPUC002 inhibits proliferation and induces apoptosis in multiple myeloma cells by stabilizing p53 and inhibiting the STAT3 signaling pathway, suggesting potential therapeutic targets for multiple myeloma treatment.
Multiple myeloma has always been an important health problem in human beings due to its high morbidity, high mortality, and lack of effective therapeutic drugs. This study investigated the anticancer effect and mechanism of the newly synthesized small molecule compound CPUC002 on multiple myeloma. Our results confirmed that CPUC002 inhibited proliferation and induced G0/G1 cell cycle arrest in multiple myeloma cells. Moreover, CPUC002 also induced apoptosis by mitochondrial pathway and exogenous pathway. In mechanism, CPUC002 triggered apoptosis by stabilizing p53 in NCI-H929 cells which expressed wt-p53. Knockdown of p53 partially suppressed CPUC002-induced apoptosis. This suggests that there are other molecular mechanisms underlying CPUC002's antitumor effect. Further studies showed that the CPUC002 also inhibited the STAT3 signaling pathway, while knockdown of STAT3 abolished CPUC002-induced apoptosis and cell cycle arrest. In vivo, CPUC002 has significant antitumor activity through the same mechanism as our in vitro studies, and is highly safe in xenograft models. Together these findings indicate that CPUC002 induces apoptosis and G0/G1 cell cycle arrest in multiple myeloma cells by stabilizing p53 and inhibiting the STAT3 signaling pathway.
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