Synthesis and Evaluation of a Novel Small-molecule Compound as an Anticancer Inhibitor of CD147.
- Author:
Zhi Guang FU
1
,
2
;
Yan WANG
3
;
Shuang WANG
4
;
Dan SHAO
4
;
Li TIAN
5
;
Yun Xia LI
6
;
Jian Li JIANG
7
;
Zhi Nan CHEN
7
;
Ning WEN
8
Author Information
- Publication Type:Journal Article
- Keywords: Antigens; Antineoplastic agents; Apoptosis; CD147
- From: Biomedical and Environmental Sciences 2019;32(9):673-686
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:Cancer is a serious threat to human health. Despite extensive research on cancer treatment, there is a growing demand for new therapies. CD147 is widely involved in tumor development, but it is unclear whether cancer cell malignancy is affected by CD147 expression level. The first compound (AC-73) targeting CD147 could only act on advanced tumors and inhibit metastasis. Therefore, new compounds with better anticancer activity should be explored.
METHODS:Wst-1 assays were used to confirm the effect of novel compounds on proliferation. Apoptosis tests were used to evaluate their proapoptotic capacity. A nude mouse model was used to demonstrate in vivo anticancer activity and safety of the compounds. Western blots were used to suggest a molecule mechanism.
RESULTS:There is a positive correlation between CD147 expression and tumor cell proliferation. A new compound, HA-08, was synthesized and proved to be more active than AC-73. HA-08 could inhibit cancer cell viability and promote cancer cell apoptosis both in vitro and in vivo. HA-08 induces cancer apoptosis, mainly by disrupting the CD147-CD44 interaction and then down-regulating the JAK/STAT3/Bcl-2 signaling pathway.
CONCLUSION:Our results have clarified the tumor specificity of CD147 and its drug target characteristics. The biological profile of HA-08 suggests that this compound could be developed as a potential anticancer agent.
