Abstract:
:In the course of screening for a novel anticancer drug candidate, we previously isolated HY251 with the molecular structure of 3-propyl-2-vinyl-1,2,3,3a,3b,6,7,7a,8,8a-decahydrocyclopenta[a]indene-3,3a,7a,8a-tetraol from the roots of Aralia continentalis. The current study was designed to evaluate the detailed mechanisms of apoptotic induction of HY251 in androgen-sensitive prostate cancer LNCaP cells. TUNEL assay and Western blot analysis revealed an appreciable apoptotic induction in LNCaP cells treated with 95μM of HY251 for 24h. This apoptotic induction is also associated with cytochrome c release from mitochondria which, in turn, resulted in the activation of caspase-9 and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, we found that HY251 significantly inhibited the expression levels of androgen receptor (AR) and prostate-specific antigen (PSA) in a time-dependent manner, as well as abrogated up-regulation of AR and PSA genes with and without androgen. Therefore, we suggest that HY251, a novel androgen antagonist, may be a potent cancer chemotherapeutic candidate for the treatment of both androgen-sensitive and hormone-refractory prostate cancer.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Oh HL,Lee CHdoi
10.1016/j.bmcl.2011.01.045subject
Has Abstractpub_date
2011-03-01 00:00:00pages
1347-9issue
5eissn
0960-894Xissn
1464-3405pii
S0960-894X(11)00068-0journal_volume
21pub_type
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