Cycloartane-type sapogenol derivatives inhibit NF?B activation as chemopreventive strategy for inflammation-induced prostate carcinogenesis
Küçük Resim Yok
Tarih
2018
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier Inc.
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Chronic inflammation is associated to 25% of cancer cases according to epidemiological data. Therefore, inhibition of inflammation-induced carcinogenesis can be an efficient therapeutic approach for cancer chemoprevention in drug development studies. It is also determined that anti-inflammatory drugs reduce cancer incidence. Cell culture-based in vitro screening methods are used as a fast and efficient method to investigate the biological activities of the biomolecules. In addition, saponins are molecules that are isolated from natural sources and are known to have potential for tumor inhibition. Studies on the preparation of analogues of cycloartane-type sapogenols (9,19-cyclolanostanes) have so far been limited. Therefore we have decided to direct our efforts toward the exploration of new anti-tumor agents prepared from cycloastragenol and its production artifact astragenol. The semi-synthetic derivatives were prepared mainly by oxidation, condensation, alkylation, acylation, and elimination reactions. After preliminary studies, five sapogenol analogues, two of which were new compounds (2 and 3), were selected and screened for their inhibitory activity on cell viability and NF?B signaling pathway activity in LNCaP prostate cancer cells. We found that the astragenol derivatives 1 and 2 as well as cycloastragenol derivatives 3, 4, and 5 exhibited strong inhibitory activity on NF?B signaling leading the repression of NF?B transcriptional activation and suppressed cell proliferation. The results suggested that these molecules might have significant potential for chemoprevention of prostate carcinogenesis induced by inflammatory NF?B signaling pathway. © 2018 Elsevier Inc.
Açıklama
Anahtar Kelimeler
Astragenol, Cycloastragenol, Inflammation-induced carcinogenesis, NF?B, Prostate cancer chemoprevention, Semi-synthesis
Kaynak
Steroids
WoS Q Değeri
Scopus Q Değeri
Q2
Cilt
135
