Anti‐proliferative effect of Ca 2+ ‐activated K + channel K Ca 2.2 blocker in prostate cancer LNCaP cells

• Published in: The FASEB journal Vol. 34; no. S1; p. 1
• Main Authors: Niwa, Satomi, Kobayashi, Yuki, Tanaka, Satoshi, Ohya, Susumu
• Format: Journal Article
• Language: English
• Published: 01-04-2020
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2020.34.s1.02419

Abstract only
Androgen receptors (AR) are essential for the growth of prostate cancer (PC) cells. Androgen deprivation (castration) therapy as antiandrogens is the powerful treatments for PC. However, the most hormone‐sensitive PC patients after the powerful treatment suffer from progression to hormone‐refractory, castration‐resistant PC (CRPC). Therefore, the novel therapeutic targets are required for PC treatment. Ca
2+
‐activated K
+
(K
Ca
) channels are highly expressed in various types of cancers including prostate cancer, and high level K
Ca
channel expression is associated with high metastatic risk, poor prognosis, and lower overall survival. K
+
channel activity was measured by plasma membrane potential imaging with voltage‐sensitive fluorescent dye, DiBAC
4
(3) and whole‐cell patch clamp recordings, and intracellular Ca
2+
concentration was measured by Ca
2+
imaging with fluorescent Ca
2+
indicator, Fura 2‐AM. Of 5 K
Ca
channels, K
Ca
2.2 was predominantly expressed in human androgen‐sensitive prostate cancer LNCaP cells. The potent and selective K
Ca
2.x blocker, UCL1684‐induced depolarization reduced store‐operated Ca
2+
entry (SOCE), and LNCaP cell proliferation was suppressed by the treatment with UCL1684. Both pharmacological and siRNA‐mediated blockades of AR using antiandrogens and AR siRNA decreased the expression levels of K
Ca
2.2 in LNCaP cells, whereas the treatment with UCL1684 did not alter the expression levels of AR, suggesting that K
Ca
2.2 may work as a downstream effector of AR signaling. Of interest, the long‐term androgen deprivation for 96 hr increased the expression levels of AR and K
Ca
2.2 in LNCaP cells. These results provide K
Ca
2.2 may be a potential therapeutic candidate in advanced, recurrent hormone‐sensitive PC and CRPC.