Ursolic acid derivative FZU-03,010 inhibits STAT3 and induces cell cycle arrest and apoptosis in renal and breast cancer cells.
Advanced renal cell carcinoma and triple negative breast cancer (TNBC) are malignancies without effective therapeutics currently. Ursolic acid (UA) has been previously reported to have anti-cancer effects in multiple solid tumors. In order to develop more potent anti-cancer reagents, FZU-03,010 based on the chemical structure of UA were synthesized. The results demonstrated that, compared with UA, FZU-03,010 could suppress renal cancer cell 786-0 and TNBC cell HCC1806 cell viability more potently.  Furthermore, FZU-03,010 could induce G1 cell cycle arrest and cell apoptosis more efficiently than UA. FZU-03,010 could also inhibit signal transducer and activator of transcription 3 activation, induce the expression of cell cycle-dependent kinase inhibitors (p21 and p27) and promote cell apoptosis. In conclusion, our results suggest that the UA derivative FZU-03,010 is more potent in inhibiting cancer cell survival, and FZU-03,010 has the potential to be developed as a therapeutic for renal cell cancers and TNBCs.
Department of Urology of the First People's Hospital of Yunnan Province, Kunming 650032, China.|Medical College of Kunming University of Science and Technology, Kunming 650032, China.
Wei
W
Li
Department of Urology of the First People's Hospital of Yunnan Province, Kunming 650032, China.|Medical College of Kunming University of Science and Technology, Kunming 650032, China.
Hongxiu
H
Zhang
Department of Urology of the First People's Hospital of Yunnan Province, Kunming 650032, China.|Medical College of Kunming University of Science and Technology, Kunming 650032, China.
Mingxiu
M
Nie
Department of Urology of the First People's Hospital of Yunnan Province, Kunming 650032, China.|Yunnan University of Traditional Chinese Medicine, Kunming 650032, China.
Yanlei
Y
Tian
Department of Urology of the First People's Hospital of Yunnan Province, Kunming 650032, China.|Medical College of Kunming University of Science and Technology, Kunming 650032, China.
Xu
X
Chen
Key Laboratory of Animal Models and Human Disease Mechanisms of Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Ceshi
C
Chen
College of Chemistry, Fuzhou University, Fuzhou 350116, China.
Haijun
H
Chen
Key Laboratory of Animal Models and Human Disease Mechanisms of Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Rong
R
Liu
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010879:Piperazines; D050796:STAT3 Transcription Factor; D014315:Triterpenes; D000097245:Ursolic Acid; C000621943:FZU-03,010
FZU-03,010; STAT3; renal cell carcinoma; triple negative breast cancer; ursolic acid