New betulinic acid derivatives induce potent and selective antiproliferative activity through cell cycle arrest at the S phase and caspase dependent apoptosis in human cancer cells
Biochimie, ISSN: 0300-9084, Vol: 93, Issue: 6, Page: 1065-1075
2011
- 44Citations
- 44Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations44
- Citation Indexes44
- 44
- CrossRef39
- Captures44
- Readers44
- 44
Article Description
New semisynthetic derivatives of betulinic acid (BA) RS01, RS02 and RS03 with 18–45 times improved cytotoxic activity against HepG2 cells, were tested for their ability to induce apoptosis and cell cycle arrest in HepG2, HeLa and Jurkat cells. All the compounds induced significant increase in the population at the S phase more effectively than BA. RS01, RS02 and RS03 were also found to be potent inducers of apoptosis with RS01 being markedly more potent than BA, suggesting that the introduction of the imidazolyl moiety is crucial for enhancing the induction of apoptosis and the cell cycle arrest. The mechanism of apoptosis induction has been studied in HepG2 cells and found to be mediated by activation of the postmitochondrial caspases-9 and -3 cascade and possibly by mitochondrial amplification loop involving caspase-8. These facts were corroborated by detection of mitochondrial cytochrome c release and DNA fragmentation. Because RS01, RS02 and RS03 exhibited significant improved antitumor activity with respect to BA, they may be promising new agents for the treatment of cancer. In particular, RS01 is the most promising compound with an IC 50 value 45 times lower than BA on HepG2 cells and 61 times lower than the one found for the non-tumoral Chang liver cells.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0300908411000708; http://dx.doi.org/10.1016/j.biochi.2011.02.014; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79955054133&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/21377507; https://linkinghub.elsevier.com/retrieve/pii/S0300908411000708; https://dx.doi.org/10.1016/j.biochi.2011.02.014
Elsevier BV
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