TY - JOUR
T1 - Artepillin C overcomes apalutamide resistance through blocking androgen signaling in prostate cancer cells
AU - Ota, Atsumi
AU - Kawai, Mina
AU - Kudo, Yudai
AU - Segawa, Jin
AU - Hoshi, Manami
AU - Kawano, Shinya
AU - Yoshino, Yuta
AU - Ichihara, Kenji
AU - Shiota, Masaki
AU - Fujimoto, Naohiro
AU - Matsunaga, Toshiyuki
AU - Endo, Satoshi
AU - Ikari, Akira
N1 - Funding Information:
This study was partially supported by JSPS Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science , MEXT KAKENHI Grant Number JP 20K05751 ), research grant from Shorai Foundation for Science and Technology (to S.E.), and collaborative research grant from API Co., Ltd. (Gifu, Japan).
Funding Information:
This study was partially supported by JSPS Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science, MEXT KAKENHI Grant Number JP 20K05751), research grant from Shorai Foundation for Science and Technology (to S.E.), and collaborative research grant from API Co. Ltd. (Gifu, Japan).
Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/2
Y1 - 2023/2
N2 - Prostate cancer has a relatively good prognosis, but most cases develop resistance to hormone therapy, leading to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) antagonists and a cytochrome P450 17A1 inhibitor have been used to treat CRPC, but cancer cells readily develop resistance to these drugs. In this study, to improve the therapy of CRPC, we searched for natural compounds which block androgen signaling. Among cinnamic acid derivatives contained in Brazilian green propolis, artepillin C (ArtC) suppressed expressions of androgen-induced prostate-specific antigen and transmembrane protease serine 2 in a dose-dependent manner. Reporter assays revealed that ArtC displayed AR antagonist activity, albeit weaker than an AR antagonist flutamide. In general, aberrant activation of the androgen signaling is involved in the resistance of prostate cancer cells to hormone therapy. Recently, apalutamide, a novel AR antagonist, has been in clinical use, but its drug-resistant cases have been already reported. To search for compounds which overcome the resistance to apalutamide, we established apalutamide-resistant prostate cancer 22Rv1 cells (22Rv1/APA). The 22Rv1/APA cells showed higher AR expression and androgen sensitivity than parental 22Rv1 cells. ArtC inhibited androgen-induced proliferation of 22Rv1/APA cells by suppressing the enhanced androgen signaling through blocking the nuclear translocation of AR. In addition, ArtC potently sensitized the resistant cells to apalutamide by inducing apoptotic cell death due to mitochondrial dysfunction. These results suggest that the intake of Brazilian green propolis containing ArtC improves prostate cancer therapy.
AB - Prostate cancer has a relatively good prognosis, but most cases develop resistance to hormone therapy, leading to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) antagonists and a cytochrome P450 17A1 inhibitor have been used to treat CRPC, but cancer cells readily develop resistance to these drugs. In this study, to improve the therapy of CRPC, we searched for natural compounds which block androgen signaling. Among cinnamic acid derivatives contained in Brazilian green propolis, artepillin C (ArtC) suppressed expressions of androgen-induced prostate-specific antigen and transmembrane protease serine 2 in a dose-dependent manner. Reporter assays revealed that ArtC displayed AR antagonist activity, albeit weaker than an AR antagonist flutamide. In general, aberrant activation of the androgen signaling is involved in the resistance of prostate cancer cells to hormone therapy. Recently, apalutamide, a novel AR antagonist, has been in clinical use, but its drug-resistant cases have been already reported. To search for compounds which overcome the resistance to apalutamide, we established apalutamide-resistant prostate cancer 22Rv1 cells (22Rv1/APA). The 22Rv1/APA cells showed higher AR expression and androgen sensitivity than parental 22Rv1 cells. ArtC inhibited androgen-induced proliferation of 22Rv1/APA cells by suppressing the enhanced androgen signaling through blocking the nuclear translocation of AR. In addition, ArtC potently sensitized the resistant cells to apalutamide by inducing apoptotic cell death due to mitochondrial dysfunction. These results suggest that the intake of Brazilian green propolis containing ArtC improves prostate cancer therapy.
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U2 - 10.1016/j.abb.2023.109519
DO - 10.1016/j.abb.2023.109519
M3 - Article
C2 - 36642262
AN - SCOPUS:85146547375
SN - 0003-9861
VL - 735
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
M1 - 109519
ER -
