Potential involvement of mt1 receptor and attenuated sex steroid‐induced calcium influx in the direct anti‐proliferative action of melatonin on androgen‐responsive LNCaP human prostate cancer cells
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abstract
Melatonin, a pineal secretory product, has been shown to exert a direct anti‐proliferative action on the androgen‐sensitive LNCaP prostate cancer cell line through hitherto undefined mechanisms. In this communication, expression of mt1 melatonin receptor protein in
human prostate cancer tissues and LNCaP cells was demonstrated by
immunohisto(cyto)chemistry and western blotting, hence supporting the use
of LNCaP cell line as a model for the study of melatonin signaling in
prostate cancer cell growth. Using
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H‐thymidine incorporation assay, LNCaP cell proliferation was
inhibited by 2‐iodomelatonin, a high‐affinity melatonin receptor agonist.
Furthermore, melatonin inhibited
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H‐thymidine incorporation into LNCaP cells and attenuated
5α‐dihydrotestosterone (DHT) or 17β‐estradiol
(E2)‐induced stimulation of LNCaP cell proliferation at
physiological and pharmacological concentrations. Similar
concentration‐dependent inhibition of sex steroid‐induced stimulation of
thymidine incorporation into LNCaP cells by 2‐iodomelatonin was also
observed. Interestingly, attenuation of sex steroid‐stimulated calcium
influx into LNCaP cells by pharmacological concentrations of melatonin
was recorded, whereas 2‐iodomelatonin had no effect on cytosolic calcium
changes induced by sex steroids. In addition, proliferative and cytosolic
calcium changes were associated with inhibition of total
prostate‐specific antigen (PSA) production by LNCaP cells at high
physiological and pharmacological concentrations of melatonin. Our data
suggest that activated mt1 receptor and attenuated sex steroid‐induced calcium influx are two important mechanisms mediating the direct anti‐proliferative action of melatonin on androgen‐responsive human prostate cancer cells.
