Lycopene in the treatment of prostate cancer*
Omer Kucuk1,**, Fazlul H. Sarkar1, Wael Sakr1,
Fred Khachik2, Zora Djuric1, Mousumi Banerjee1,
Michael N. Pollak1, John S. Bertram2, and David
P. Wood, Jr.1
1Prevention Program, Barbara Ann Karmanos Cancer Institute,
Wayne State University, Detroit, MI 48201, USA; 2Joint Institute for
Food Safety and Applied Nutrition (JIFSAN), Department of Chemistry
and Biochemistry, University of Maryland, College Park, MD 20742, USA;
3Department of Medicine, McGill University and Jewish General Hospital,
Montreal, Quebec H3T 1E2, Canada; 4Cancer Research Center of Hawaii,
University of Hawaii, Honolulu, HI 96813, USA
Abstract: Dietary intake of lycopene is associated
with reduced risk of prostate cancer (PCa). We conducted a clinical
trial in men with prostate cancer to investigate the biological and
clinical effects of lycopene supplementation. Twenty-six men with prostate
cancer were randomly assigned to receive a lycopene supplement or no
supplement for three weeks before radical prostatectomy. Subjects in
the intervention group (n = 15) were instructed to take a tomato oleoresin
extract soft gel capsule (Lyc-O-Mato®, LycoRed Company, Beer Sheva,
Israel) containing 15 mg lycopene, 1.5 mg phytoene, 1.5 mg phytofluene,
and 5 mg tocopherol twice daily with meals. Prostatectomy specimens
were evaluated for pathologic stage, Gleason score, volume of cancer,
and extent of high-grade prostatic intraepithelial neoplasia (HGPIN).
Biomarkers of cell proliferation and apoptosis were assessed by Western
blot analysis in benign and cancerous tissue samples obtained from the
prostatectomy specimens. Oxidative stress was assessed by measuring
the peripheral blood lymphocyte DNA oxidation product 5-hydroxymethyl-deoxyuridine
(5-OH-mdU). Plasma levels of lycopene, insulin-like growth factor-1
(IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), and
prostate-specific antigen (PSA) were measured at baseline and after
three weeks of study period. After the intervention, more men in the
intervention group had smaller (<4 cc) tumors, organ-confined disease
without involvement of surgical margins or extra-prostatic tissues,
and focal involvement of the prostate with HGPIN compared to the control
group. Mean plasma PSA levels were lower in the intervention group compared
to the control group. This pilot study suggests that a tomato extract
containing lycopene and other tomato carotenoids and phytochemicals
may have a potential role in the treatment of prostate cancer. Larger
clinical trials are necessary to definitively address potential uses
of lycopene or tomato extract in the prevention or treatment of prostate
cancer.
** Corresponding author.
*Lecture presented at the 13 th International Symposium
on Carotenoids, Honolulu, Hawaii, USA, 6-11 January 2002.
Other lectures are published in this issue, pp. 1369-1477.