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Alotaibi et al.                                                                                                                                                                        Papaya seeds effect prostate cancer

           also been characterized on  T-cell lines, Burkitt’s   toxicity and  teratogenicity which  could  affect
           lymphoma cell lines, chronic myelogenous leukemia   pregnancy, implantation,  and gestation.  However,
                                                                                                  [39]
           cell line, cervical carcinoma cell line, hepatocellular   another study reported that low dose aqueous crude
           carcinoma  cell  lines,  lung  adenocarcinoma  cell  line,   extract of papaya seeds did not adversely affect
           pancreatic epithelioid carcinoma cell line 1, pancreatic   prenatal development, whereas high doses of papaya
           adenocarcinoma cell line, mesothelioma cell lines,   extracts resulted in abortifacient property indicating
           plasma  cell  leukemia  cell  line,  anaplastic  large  cell   that papaya toxicity can adversely affect the fetus.
                                                                                                            [40]
           lymphoma cell line, breast adenocarcinoma cell line   These studies suggest that  papaya has wide range
           (MCF-7), and mesothelioma cell line.  Other studies   of activities on cellular  targets in male reproductive
                                            [34]
           have shown effect of the aqueous extract of papaya   system.  We,  therefore, tested the effect  of  papaya
           seeds on human kidney epithelial cells, human colon   seeds on prostate cancer cells.
           epithelial  cells,  human  lung  fibroblasts,  and  human
           pancreatic cells.  Interestingly no human clinical   Unripe  papaya contains white seeds whereas  ripe
                          [35]
           trials were performed  as  yet; however,  survival  was   papaya  contains black seeds.  The different color
           observed in patients with lung cancer, stomach     of seeds indicates  that as papaya  matures its
           cancer, breast cancer, pancreatic cancer, liver cancer,   compositions changes. The presence and absence of
           and blood cancer after drinking papaya leaf extract.    different compounds in papaya seeds, therefore, may
                                                         [21]
           One  report  suggested  that  papaya  can  be  effective   have different biological properties. We used hexane,
           against prostate cancer because of its lycopene    methanol, and water to extract compounds of different
           content;  however, to our knowledge no study has   chemical nature.  The hexane was used to  extract
                  [36]
           been performed to test the effect of papaya on prostate   non-polar  compounds. During this study we did not
           cancer. Furthermore, water extracts from both white   see any effect of hexane extract from either black or
           and  black  seeds  exhibited  cytotoxic  effects  on  non-  white seeds on prostate cancer cells. However, it has
           cancerous  undifferentiated  3T3  fibroblasts  whereas   been shown that hexane extract of the papaya seed
           only methanolic white seeds extracts have a marginal   was highly effective in inducing apoptosis or cell death
           effect  and  hexane  seeds  extracts  has  no  cytotoxic   in leukemic HL-60 cells.  Papaya seeds contain
                                                                                     [23]
           effects. The cytotoxic effect (15%) in the methanolic   contained  considerable  amount of oil (27.0%),
                                                                                                            [41]
           extracts from white seeds occurred at 250  µg/mL   comprising  45.9% of oleic  acid, 24.1% of palmitic
           concentration which is about 10 times higher than a   and 8.52% of stearic acid.  Among phytochemicals,
                                                                                      [28]
           50% inhibition which was observed only 25 µg/mL of   the major constituent is benzyl  isothiocyanate
           methanolic  black  seeds  extract.  Typically  all  cancer   (99.36%).  The apoptotic effect of papaya seeds on
                                                                       [27]
           drugs exhibit some degree of cytotoxic effects on   HL-60 cells were comparable to  those of  authentic
           normal cells.  Although deviated from normal path,   benzyl  isothiocyanate.   However,  lack of  hexane
                                                                                  [27]
           many pathways for cellular replication and repair are   effect on prostate cancer cells suggest that benzyl
           similar  between  cancer  and  normal  cells.  However,   isothiocyanate may not has effect in these cells.
           as cancer cells divide more rapidly than normal cells,
           the cytotoxic drugs more selectively kill cancer cells   Our  data  indicate  that  methanol  extract  from  black
           whereas the normal cells are able to adapt and recover   seeds was effective in inhibiting cell proliferation
           from toxicity. [37]                                of prostate cancer cells whereas the methanol
                                                              extract from white seeds extract was not effective.
           We hypothesized that papaya  seeds  may possess    Alcoholic extracts are commonly used to extract
           anticancer activity on prostate cancer because of its   phytochemicals as it solubilize most of the polyphenols
           effects  on male reproductive system.  The aqueous   including flavonoids and alkaloids. [42,43]  The Phenolic
           extracts from papaya seed have been reported to    compounds are a main class of secondary metabolites
           reversibly  decrease the testicular weight  and to   in plants and possess a number of potent biological
           suppress spermatogenesis, and fertility in rats.  This   activities including anti-oxidation, anti-cancer,  anti-
                                                     [38]
           study suggested that water extract of papaya  seeds   bacterial, and immune modulating activities. [44]  We
           suppresses  the activities  of steroidogenic  enzymes   found that black seed extract have almost 2.5 times
           in the testis of  rats,  and that  this may contribute to   more polyphenolic contents then white seeds. It is,
           reversible suppression of spermatogenesis, a property   however, not known what compound is predominantly
           that gives a possible  male contraceptive potential.    present in black versus white seeds. It is, therefore,
                                                         [38]
           Other studies have shown that the seed extract resulted   difficult to predict a tentative active compound in our
           in a significant dose dependent suppression of cauda   methanolic extract that resulted in prostate cancer cell
           epididymal sperm motility coinciding with a decrease   growth inhibition. Further experiments are required to
           in sperm  count  and viability  with no developmental   perform a comparative analysis of phytochemicals
            166                                                                  Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ August 28, 2017
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