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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