Araticum (Annona crassiflora Mart.) by-products suppress cell proliferation and induce apoptosis particularly in androgen-dependent prostate cancer cell lines

Abstract

Prostate cancer is the second most diagnosed type of cancer in men. The araticum (Annona crassiflora Mart.) is a fruit found in natural areas of the Brazilian cerrado, and its by-products contain a variety of compounds that have already demonstrated positive effects on cancer. To this end, we evaluated the in vitro antioxidant capacity of the extract of the peel and seed of the A. crassiflora. In addition, we investigated its antiproliferative effects and the possible mechanisms involved in inducing apoptosis in androgen-dependent and androgen-independent prostate cancer cells. The extract of A. crassiflora peel showed a high content of total phenolic compounds, reaching 222.44 mg GAE/g fdw, while the seed recorded a considerably lower value of 26.49 mg GAE/g fdw. These results indicate that the peel has a higher antioxidant capacity compared to the seed, probably due to its high content of phenolic compounds. Both extracts reduced the viability of prostate cancer cells, with the seed proving more effective. The IC50 of the seed extract was significantly lower in the PC-3 cells, presenting an IC50 of 33.24 μg/mL, 30.70 μg/mL and 24.86 μg/mL, for 24, 48 and 72 h respectively, compared to that of the peel. The peel extract showed IC50 of 277 μg/mL, 225 μg/mL and 67.30 μg/mL for the same periods. In 22Rv1 cells, the IC50 of the seed extract showed lower values, presenting IC50 of 12.64 μg/mL, 6.07 μg/mL and 5.12 μg/mL for 24, 48 and 72 h, respectively. However, the peel extract showed IC50 of 77.36 μg/mL, 42.92 μg/mL and 48.16 μg/mL for 24, 48 and 72 h. Both extracts showed a more pronounced effect on LNCaP cells. At 24 h, the IC50 of the seed extract was lower (IC50 of 22.87 μg/mL) than that of the peel extract (IC50 of 47.51 μg/mL) for LNCaP cells. However, after 48 h of treatment, the peel extract showed a decrease in IC50 of 17.64 μg/mL and the seed extract 21.13 μg/mL. However, after 72 h the seed extract was more effective in reducing cell viability with an IC50 of 6.51 μg/mL in contrast the peel showed IC50 of 11.50 μg/mL. The seed extract had a significant effect on apoptosis induction in LNCaP, increasing the protein levels of Bax, procaspase-3, caspase-9 and caspase-8, while reducing Bcl-2 and Bcl-xL expression. The seed extract also decreased the androgen receptor and PCNA levels in 22Rv1 and LNCaP cells, suggesting a possible antiproliferative mechanism mediated by the modulation of these proteins.

Keywords: Bioactive compounds; Brazilian fruit; Cytotoxic; Tumor.