Melatonin and prostate cancer

Melatonin and prostate cancer

Stephen Y. W. Shiu
Towards rational and evidence-based use of melatonin in prostate
cancer prevention and treatment
Journal of Pineal Research (OnlineEarly Articles).
Published article online: 19 Apr 2007
doi:10.1111/j.1600-079X.2007.00451.x
< * w w w .blackwell-synergy . com /doi/abs/10.1111/j.1600-079X.2007.00451.x>

"Abstract: Prostate cancer is a public health problem of the
elderly men. It has been estimated that one in six men will
develop prostate cancer in his lifetime in the USA. There is
thus a huge clinical demand for effective therapies for the
prevention and treatment of the disease. Here, the scientific
evidence supporting the effectiveness of melatonin in
inhibiting the development and progression of prostate cancer
is reviewed. The rational use of melatonin in prostate cancer
prevention, stabilization of clinically localized favourable-
risk prostate cancer and palliative treatment of advanced or
metastatic tumour is discussed within the context of the
molecular pathogenesis of the disease."

Tam CW, Mo CW, Yao KM, Shiu SY.
Signaling mechanisms of melatonin in antiproliferation of
hormone-refractory 22Rv1 human prostate cancer cells: implications for
prostate cancer chemoprevention.
J Pineal Res. 2007 Mar;42(2):191-202.
PMID: 17286752 [PubMed - indexed for MEDLINE]
doi:10.1111/j.1600-079X.2006.00406.x
< * w w w .blackwell-synergy . com /doi/abs/10.1111/j.1600-079X.2006.00406.x>

"... Taken together with the known molecular mechanisms of
prostate cancer progression and transition to androgen
independence, our data provide strong support for melatonin
to be a promising small-molecule useful for prostate cancer
primary prevention and secondary prevention of the
development and progression of hormone refractoriness."

Pukkala E, Ojamo M, Rudanko SL, Stevens RG, Verkasalo PK.
Does incidence of breast cancer and prostate cancer decrease with
increasing degree of visual impairment.
Cancer Causes Control. 2006 May;17(4):573-6.
PMID: 16596312 [PubMed - indexed for MEDLINE]
DOI: 10.1007/s10552-005-9005-6
< * w w w .springerlink . com /content/m658956088146627/>

"... CONCLUSIONS: Our findings add to the suggestive
epidemiological evidence for a decreased risk of hormone-
related cancers in people with visual impairment and,
consequently, a relationship between visible light at night
and breast cancer risk. The result is strongly against the
hypothesis of a systemic protective effect related lack of
visible light."

Sainz RM, Mayo JC, Tan DX, Leon J, Manchester L, Reiter RJ. Melatonin
reduces prostate cancer cell growth leading to neuroendocrine
differentiation via a receptor and PKA independent mechanism.
Prostate. 2005 Apr 1;63(1):29-43.
PMID: 15378522 [PubMed - indexed for MEDLINE]
DOI: 10.1002/pros.20155
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15378522>
< * w w w 3.interscience.wiley . com /cgi-bin/abstract/109629497/ABSTRACT?CRETRY=1&SRETRY=0>
< * w w w 3.interscience.wiley . com /cgi-bin/fulltext/109629497/PDFSTART>
(full text PDF file)

"... CONCLUSIONS: The treatment of prostate cancer cells with
pharmacological concentrations of melatonin influences not
only androgen-sensitive but also androgen-insensitive
epithelial prostate cancer cells. Cell differentiation
promoted by melatonin is not mediated by PKA activation
although it increases, in a transitory manner, intracellular
cAMP levels. Melatonin markedly influences the proliferative
status of prostate cancer cells. These effects should be
evaluated thoroughly since melatonin levels are diminished in
aged individuals when prostate cancer typically occurs. ..."

Shiu SY, Law IC, Lau KW, Tam PC, Yip AW, Ng WT.
Melatonin slowed the early biochemical progression of
hormone-refractory prostate cancer in a patient whose prostate tumor
tissue expressed MT1 receptor subtype.
J Pineal Res. 2003 Oct;35(3):177-82.
PMID: 12932201 [PubMed - indexed for MEDLINE]
doi:10.1034/j.1600-079X.2003.00074.x
< * w w w .blackwell-synergy . com /doi/abs/10.1034/j.1600-079X.2003.00074.x>

"... This report validates melatonin's oncostatic action on
prostate cancer and the potential involvement of MT1 receptor
subtype in the attendant antiproliferative signal
transduction as suggested by recent preclinical laboratory
findings in a human."

Xi SC, Siu SW, Fong SW, Shiu SY.
Inhibition of androgen-sensitive LNCaP prostate cancer growth in vivo
by melatonin: association of antiproliferative action of the pineal
hormone with mt1 receptor protein expression.
Prostate. 2001 Jan 1;46(1):52-61.
PMID: 11170132 [PubMed - indexed for MEDLINE]
DOI: 10.1002/1097-0045(200101)46:1<52::AID-PROS1008>3.0.CO;2-Z
< * w w w 3.interscience.wiley . com /cgi-bin/abstract/76510375/ABSTRACT>
< * w w w 3.interscience.wiley . com /cgi-bin/fulltext/76510375/PDFSTART>
(full text PDF file)

"... CONCLUSIONS: The antiproliferative action of melatonin
on LNCaP tumor growth was demonstrated in vivo, and its
association with mt1 receptor protein expression suggests the
potential involvement of the receptor in the antitumor
activity of the pineal gland hormone. ..."

Marelli MM, Limonta P, Maggi R, Motta M, Moretti RM.
Growth-inhibitory activity of melatonin on human androgen-independent
DU 145 prostate cancer cells.
Prostate. 2000 Nov 1;45(3):238-44.
PMID: 11074526 [PubMed - indexed for MEDLINE]
DOI: 10.1002/1097-0045(20001101)45:3<238::AID-PROS6>3.0.CO;2-W
< * w w w 3.interscience.wiley . com /cgi-bin/abstract/75001001/ABSTRACT>
< * w w w 3.interscience.wiley . com /cgi-bin/fulltext/75001001/PDFSTART>
(full text PDF)

"... CONCLUSIONS: Melatonin exerts a direct oncostatic
activity on human androgen-independent prostate cancer cells,
by affecting cell cycle progression. This activity seems to
be mediated by nuclear, but not by membrane, receptors. ..."

Moretti RM, Marelli MM, Maggi R, Dondi D, Motta M, Limonta P.
Antiproliferative action of melatonin on human prostate cancer LNCaP
cells.
Oncol Rep. 2000 Mar-Apr;7(2):347-51.
PMID: 10671684 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10671684>

"... These results indicate that melatonin, at nanomolar
concentrations, exerts a direct antiproliferative action on
androgen-dependent prostate cancer cells, significantly
affecting their distribution throughout the cell cycle.
Membrane receptors do not seem to be involved in the
oncostatic action of the pineal gland hormone."

Gilad E, Laufer M, Matzkin H, Zisapel N.
Melatonin receptors in PC3 human prostate tumor cells.
J Pineal Res. 1999 May;26(4):211-20.
PMID: 10340723 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10340723>

"... These results provide the first demonstration of direct
interaction of melatonin with hormone-insensitive prostate
tumor cells. The melatonin receptors in the PC3 cells are
coupled to pertussis toxin-sensitive G proteins to induce
cell density-dependent changes in cGMP, cAMP, and cell
growth."

Feychting M, Osterlund B, Ahlbom A.
Reduced cancer incidence among the blind.
Epidemiology. 1998 Sep;9(5):490-4.
PMID: 9730026 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9730026>

Bartsch C, Bartsch H, Schmidt A, Ilg S, Bichler KH, Fluchter SH.
Melatonin and 6-sulfatoxymelatonin circadian rhythms in serum and
urine of primary prostate cancer patients: evidence for reduced pineal
activity and relevance of urinary determinations.
Clin Chim Acta. 1992 Aug 31;209(3):153-67.
PMID: 1395046 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=1395046>





--
Matti Narkia