Inhibition of Castration-Sensitive LNCaP, Castration-Resistant TRAMP-C2, and Bone-Metastatic C4-2B Prostate Cancer Cell Growth by an Alpha-Tomatine Tomato Extract: In Vitro and In Vivo Study

Currently, hormonal therapy is the main treatment option for advanced prostate cancer; however, a certain number of cases progress to metastatic, castration-resistant prostate cancer. Therefore, we designed in vitro and in vivo studies of a new molecular targeted therapy using alpha-tomatine (α-tomatine), a glycoalkaloid extracted from tomatoes, for the growth inhibition of both castration-sensitive human LNCaP and castration-resistant mouse TRAMP-C2 and metastatic human C4-2B prostate cancer cell lines. In vitro, α-tomatine supplementation showed a dose-dependent decrease in the proliferation potential of all prostate cancer cells at concentrations ranging from 1.0 to 5.0 μg/mL, as well as a decrease in migration and invasion abilities at concentrations ranging from 1.0 to 2.5 μg/mL, which was sustained throughout the 72 hours post-treatment (p < 0.050). Furthermore, flow cytometry demonstrated that α-tomatine at 2.5 μg/mL enhanced the incidence of apoptosis in TRAMP-C2 cells at 48 hours post-treatment (p < 0.010). In vivo, TRAMP-C2 cells were subcutaneously implanted in C57BL/6 mice. Then, at a 10-mm diameter, single-time intratumoral injection of 1.0 µg/body α-tomatine was performed. Longitudinal follow-up identified a time-dependent tumor growth inhibition at 3-4 (p<i> </i>< 0.050), 5-7 (p < 0.010), and 8-10 (p < 0.001) days after the administration of α-tomatine. In summary, α-tomatine has the potential to block the proliferation, migration, and invasion of both castration-sensitive and castration-resistant prostate cancer (CRPC) types, even with metastatic cell lines. Further investigation is warranted to clarify the pharmacological action and molecular mechanism of α-tomatine's effects on prostate cancer cells.