Lantabetulic acid derivatives induce G1 arrest and apoptosis in human prostate cancer cells.
Ten new lantabetulic acid (1) derivatives 2-11 were synthesized and their cytotoxicities against human prostate cancer cells were evaluated. PC3 cells treated with 10 μM 8 exhibited the most potent G1 phase arrest. In addition, 10 μM 8 markedly decreased the levels of cyclin E and cdk2 and caused an increase in the p21 and p27 levels, while 20 μM 8 mainly led to cell death through the apoptotic pathway, which correlated with an increase in reactive oxygen species levels, decreased expression levels of Bcl-2 and caspase-8, the induction of mitochondrial changes, and decreased levels of cytochrome c in mitochondria. The dual action of 8 could provide a new approach for the development of chemotherapeutic drugs.
Faculty of Fragrance and Cosmetics, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
Kai-Wei
KW
Lin
Zih-You
ZY
Lin
A-Mei
AM
Huang
Jing-Ru
JR
Weng
Ming-Hong
MH
Yen
Shyh-Chyun
SC
Yang
Chun-Nan
CN
Lin
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014315:Triterpenes / Q000138:chemical synthesis / Q000494:pharmacology*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D017382:Reactive Oxygen Species; D014315:Triterpenes
Apoptosis; Cytotoxicity; G1 arrest; Lantabetulic acid; Synthesis