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Alotaibi et al.                                                                                                                                                                        Papaya seeds effect prostate cancer

           flavus,  Candida albicans and  Penicillium  citrinium. [30]   In  addition to  various biological activities described
           Furthermore, treatment of methanolic  extract of the   above, anticancer activities have been demonstrated
                                                                                                            [21]
           papaya seeds in rats induced gastroprotection without   by papaya extracts in a number of in vitro studies.
           signs of toxicity. This effect seems to involve sulfhydryl   Papaya juice and pure lycopene, a component present
                                                              in papaya, caused cell death in the liver cancer cell line,
           compounds, increased mucus,  and reduced gastric   Hep G2, with the half maximal inhibitory concentration
           acidity. [31]                                      (IC 50) of 20 µg/mL and 22.8 µg/mL, respectively.
                                                                                                            [22]
                                                              Papaya seed extract also exhibited anticancer activity
                                                              in acute promyelotic leukemia HL-60 cells at IC 50 of
                                                              20 µg/mL whereas papaya pulp extract did not have
                                                              any effect even at a concentration of 100 µg/mL.  In
                                                                                                          [23]
                                                              contrast,  Garcia-Solis  et al.  observed  that papaya
                                                                                       [32]
                                                              pulp inhibited of proliferation of MCF-7 cells after 72-h
                                                              treatment. In our studies, we have observed  almost
                                                              50% growth inhibition at 25 µg/mL of methanol seeds
                                                              extract on PC-3 cells. These results are in the similar
                                                              range of concentration as shown by other studies. [22,23]
                                                              This effect does not appear to be due to residual
                                                              methanol contamination because the methanolic
                                                              seeds extract after dryness under nitrogen  gas was
                                                              subjected to freeze drying under vacuum over night to
                                                              ensure  complete removal  of methanol.  Furthermore,
                                                              from both seeds extracts only methanolic white seeds
                                                              extract has a small (15% inhibition) effect (P < 0.05) on
                                                              3T3L1 fibroblasts [Figure 3], again suggesting unlikely
                                                              effect of methanol in the extracts.

                                                              The effect of papaya on cancer growth inhibition
                                                              are  further  evident  from  studies  performed
                                                              by Morimoto  et al.  who patented the extracts
                                                                                 [33]
                                                              of different parts of papaya for the prevention,
                                                              treatment, or improvement of many types of cancer,
                                                              including stomach, lung, pancreatic, colon, liver,
                                                              ovarian,  neuroblastoma,  lymphoma,  leukemia,  and
                                                              other blood cancers. Effect of papaya leaves have





















           Figure 3: The effect of Papaya seeds extract on non-cancerous   Figure 4: Total phenolic contents in black and white papaya seeds.
           undifferentiated 3T3L1 fibroblasts. Cells (10,000/well) were   The phenolic contents in black and white extracts were determined
           incubated with different concentration of water (A), methanol   using a Folin Ciocalteu reagent (Sigma Chem. Co., St. Louis, MO)
           (B), and hexane (C) extracts of papaya white or black seeds in a   and the total phenolic content was calculated from a calibration
                          o
           CO 2  incubator at 37  C for 24 h. After treatment, cell viability was   curve using Gallic acid as a standard, and the result are expressed
           determined using a WST-1 assay. Results are expressed as mean   as mg Gallic acid equivalent per g dry weight of sample. *Significant
           ± SD for at least 3 replicates. *Significant differences between   differences between black seeds and white seeds were reported as
           treated and untreated groups were reported as *P < 0.05  *P < 0.05
                           Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ August 28, 2017        165
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