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Gene & Protein in Disease                                         Natural carotenoids prevent prostate cancer



            is necessary to highlight that carotenoids are susceptible   concentrations inhibited the growth of LNCaP PCa cells.
            to oxidation and degradation induced by heat or light, a   Although lycopene, phytoene, and phytofluene are effective
            phenomenon known as photooxidation.  Consequently,   only at high concentrations, their co-administration at low
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            experimental evidence should be interpreted with caution.  concentrations of approximately 0.3 μM demonstrated a
              Laboratory studies conducted on mouse models and   synergistic effect. 110
            cell lines have revealed that  β-carotene and lycopene   Interestingly, lycopene displays a variable anti-
            possess apoptotic effects on PCa cells, accompanied by   proliferative profile depending on the source of
            reduced cellular accumulation and adhesion. Specifically,   consumption. Lycopene derived from tomato paste and
            the administration of lycopene at concentrations exceeding   tomato extract has been shown to reduce the proliferation
            1.25 μM resulted in reduced PCa cell growth by inhibiting   of PCa cells in the G0/G1 and G2/M phases. Conversely,
            the expression of NF-κB, TP53, BAX, and BCL-2      lycopene derived from tomato sauce and ketchup leads to
            transcripts. Conversely, concentrations below 0.5  μM   decreased proliferation of PCa cells in the G0/G1 phase
            demonstrated no effect, thus explaining the discrepancies   and increased proliferation in the S and G2/M phases.
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            observed in previous studies. 101,102  Immunofluorescence   Overall, these results suggest the potential benefits of
            staining results further demonstrated that lycopene   incorporating lycopene into the diets of prostate and breast
            inhibits TNFα-induced NF-κB p65 nuclear translocation   cancer patients.  It is important to note that these results
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            in the PC3 and MDA-MB-231 cell lines, which serve   are sensitive to the TME and tissue specificity. Clinton
            as  models  for androgen-dependent PCa  and  hormone-  et al. demonstrated that carotenoids exhibit variable
            independent  breast  cancer,  respectively.  Notably,  the   distribution due to different transport mechanisms. For
            reduction in NF-κB activity was most prominent in the   instance,  lycopene  tends  to  accumulate  in  the  prostate,
            PC3 cell line compared to PCa xenografts.  In addition   whereas zeaxanthin is mainly distributed to adipose tissue
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            to the NF-κB p65 factor, androgen-dependent PCa    and the ovaries. Evidence indicates that carotenoids have
            appears to be regulated by the peroxisome proliferator-  a propensity to accumulate in tissues with low-density
            activated  receptor  gamma  (PPARγ)  and  liver  X  receptor   lipoprotein (LDL) receptors, such as adrenals, testes, and
            alpha (LXRα). Lycopene administration (2.5 – 10 μM) has   liver.  However, intracellular metabolic pathways also
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            been demonstrated to upregulate these receptors, thereby   play a key role in the accumulation of carotenoids. Further
            inhibiting the proliferation of PCa cells.  Furthermore,   pre-clinical and clinical studies are necessary to fully
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            incubation studies demonstrated that 1.15  μmol/l of   interpret the profile and effects of carotenoids on Pca, both
            lycopene reduced PCa cell mobility by 40% and inhibited   in vitro and in vivo.
            cell adhesion in concentrations exceeding 1.15 μmol/l. 105
              The majority of intervention studies investigate the   3. Potential use of carotenoids in patients
            synergistic chemopreventive effects of carotenoids, as   diagnosed with PCa
            administering a single compound has proven to be   Several trials have demonstrated the beneficial effects of
            unsuccessful. In fact, studies by The Alpha-Tocopherol   lycopene supplementation in patients diagnosed with
            Beta Carotene Cancer Prevention Study Group and    PCa. Randomized phase II clinical trials have indicated a
            Omenn et al. demonstrated that supplemental β-carotene   reduced PCa incidence following nutritional intervention
            had a negative effect on smokers with lung cancer and   with 15 mg of lycopene administered twice a day to PCa
            colorectal adenoma. 106,107  However, when administered in   patients before radical prostatectomy for a duration of
            combination with polyphenols, vitamin E, and vitamin   3  weeks. Prostate-specific antigen (PSA) levels, clinical
            A,  β-carotene  exhibited synergistic  effects  by reducing   risk assessments, and follow-up increased by 14% in the
            oxidative stress and the formation of lipid hydroperoxides   control group, whereas they declined by 18% in the group
            and malondialdehyde.  Vitamin A enhances the       that received lycopene. In addition to reductions in PSA
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            antioxidant activity of β-carotene by eliminating oxygen   levels and clinical risk assessments, the intervention group
            radicals. Due to their lipophilic nature, carotenoids play a   also exhibited a lower prevalence of tumors with a volume
            key role in protecting cellular membranes by eliminating   of  <4  mL  compared  to the  control  group.  Specifically,
            peroxyl  radicals  generated  during  lipid  peroxidation.   tumors of this size were present in 84% of the intervention
            Another study focusing on patients with benign breast   group and 45% of the control group.  In another trial,
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            disease followed by premenstrual mastalgia demonstrated   54  patients  with histologically proven  metastatic  PCa
            positive  results  with  no  side  effects  from  high-dosage   were enrolled. The two treatment groups respectively
            supplementation of  β-carotene and retinol.  Similarly,   treated with orchidectomy alone and orchidectomy plus
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            a combination of lycopene with phytoene, phytofluene,   lycopene, each involving 27 patients. On the day of surgery,
            1,25-dihydroxyvitamin  D3, and  retinoic  acid  at  low   administration of 2 mg of lycopene started twice a day. PSA


            Volume 3 Issue 1 (2024)                         9                        https://doi.org/10.36922/gpd.2827
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