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Page 6 of 15                           Hadadi et al. J Cancer Metastasis Treat 2018;4:25  I  http://dx.doi.org/10.20517/2394-4722.2018.22



                                                           Water extract (mg/mL)
                                                           Methanol extract (mg/mL)
                                                           Ethanol extract (mg/mL)

                                     % Inhibition of DPPH












                                                Leaves              Skin              Pulp              Seed

               Figure 3. Anti-oxidation capacity of papaya fractions. The anti-oxidation activity in papaya extracts was determined by using 2,
               2-Diphenyl-1-picrylhydrazyl (DPPH) method. The data is reported as % inhibition of DPPH oxidation. Results are mean ± SD for at least
               3 experiments. The results of methanol and ethanol extracts were compared to that of the water extracts. The significant differences, as
               marked “*”, are reported at P < 0.05


               The effect of methanol extract from leaves, skin, pulp and seeds is shown in Figure 4B. The data indicate that
               none of the papaya fractions has any significant effect on cell viability of MDA-MB-231 breast cancer cells.


               The effect of ethanol extract from leaves, skin, pulp and seeds is shown in Figure 4C. The extract from
               leaves, skin, and pulp has no significant effect; however, seed extract reduced cell viability starting at
               75 mg/mL. The cell viability was reduced significantly by 20% (P < 0.05) at the highest concentration of
               250 mg/mL.

               Effect of papaya leaves and seeds extract on MCF-7 breast cancer cells
               As we found from our previous experiment, neither the water, methanol nor ethanol extracts from pulp
               and skin had any effect on breast cancer cells; however, leaves and seeds showed effects on cell proliferation.
               We, therefore, carried out subsequent experiments on the extracts from leaves and seeds only. The effect of
               water extract from leaves and seeds is shown in Figure 5A. The extract from seeds, has no significant effect;
               however, leaves extract reduced cell viability significantly by 30% (P < 0.05) at the highest concentration of
               250 mg/mL.


               The effect of methanol extract from leaves and seeds is shown in Figure 5B. The data indicate that none of
               the papaya fractions has any significant effect on cell viability of MCF-7 breast cancer cells.


               The effect of ethanol extract from leaves and seeds is shown in Figure 5C. Similarly, our data indicate that
               none of the papaya fractions has any significant effect on cell viability of MCF-7 breast cancer cells.

               Effect of papaya leaves and seeds extract on SK-Br-3 breast cancer cells
                                                                               -
               We performed further experiments to test the effect of papaya extracts in ER/Her-2  breast cancer using SK-
                                                                                     +
               Br-3 cells. As explained above, we only tested extracts from leaves and seeds on these cells.

               The effect of water extract from leaves and seeds is shown in Figure 6A. The extract from seeds has no
               significant effect except at the highest concentration (250 mg/mL) where cell viability is reduced by 25 % (P <
               0.05). However, leaf extract reduced cell viability in a dose-dependent manner starting at 10 mg/mL. The cell
               variability was reduced significantly by 50% (P < 0.05) at the highest concentration of 250 mg/mL.
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