Growth inhibitory activity of lemnabourside on human prostate cancer cells.
Induction of apoptosis and androgen ablation are two major approaches for treating human prostate carcinoma. In a study of the bioactive components of the soft coral Nephthea chabroli, we found that lemnabourside is a 5alpha-reductase inhibitor, as shown by its ability to inhibit the conversion of testosterone into the more potent dihydrotestosterone in rat prostate homogenate. The compound also inhibited the incorporation of tritiated thymidine into human prostate androgen-dependent carcinoma LNCaP cells, and thus blocking the cell proliferation (IC50 = 37.5 microM). The expression of prostate marker genes, including 5alpha-reductase, prostate-specific antigen, prostatic acid phosphatase and androgen receptor, and the anti-apoptotic bcl-2 gene were markedly reduced, but the transcription of apoptosis-related caspase 3 gene showed a dose-dependent increase in lemnabourside-treated LNCaP cells. Immunofluorescent microscopy and flow cytometric analysis further demonstrated apoptotic changes in these cells. Taken all results together, a relatively weak 5alpha-reductase inhibitory activity on LNCaP cells (EC50 > 250 microM), and a similar growth inhibitory activity on both androgen dependent- and independent-prostate cells (IC50 approximately 37.5 microM) indicated that caspase-3 apoptosis pathway is one of the possible antiproliferative activities mediated by lemnabourside.
Liu
W K
WK
Department of Anatomy, The Chinese University of Hong Kong, Shatin, New Territories. ken-liu@cuhk.edu.hk
Wong
N L Y
NL
Huang
H M
HM
Ho
J K C
JK
Zhang
W H
WH
Che
C T
CT
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000135:Acid Phosphatase / Q000096:biosynthesis / Q000235:genetics; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000096:biosynthesis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D004224:Diterpenes; D006027:Glycosides; D019253:Proto-Oncogene Proteins c-bcl-2; D011944:Receptors, Androgen; C447445:lemnabourside; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D000135:Acid Phosphatase; D017430:Prostate-Specific Antigen; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases