Anticancer Potential of Valencia Peanut (Arachis hypogaea L.) Skin Extract against Cervical Cancer Cells In Vitro and in Nude Mouse Xenograft Models.

This study investigated the impact of Valencia KK4-type peanut skin ethanolic extract (KK4-PSE) combined with cisplatin or 5-fluorouracil (5-FU) on HeLa cells in vitro and in xenograft models. At exposure times of 24, 48 and 72 h, KK4-PSE inhibited the growth of HeLa cells with a half maximal inhibitory concentration (IC50) of 79.43 ± 0.54, 55.55 ± 1.57 and 41.32 ± 0.74 µg/mL, respectively. Drug interactions evaluated by the Chou-Talalay method demonstrated that KK4-PSE enhanced antiproliferative activity of 5-FU against HeLa cells with combination index (CI) values of 0.49 (48 h) and 0.60 (72 h), indicating a synergistic effect, while KK4-PSE combined with cisplatin exhibited an additive effect (CI = 1.02) at 72 h, and an antagonistic effect at 24 and 48 h exposures (CI = 1.12 and 1.18, respectively). In nude mouse xenograft models, the combination of 5-FU and KK4-PSE markedly reduced HeLa tumor weights compared with the control and single agent treatments groups. The combination of KK4-PSE and 5-FU achieved greater tumor growth inhibition than that of the KK4-PSE-cisplatin combination. KK4-PSE mitigated hepatotoxicity induced by both cisplatin and 5-FU in nude mice. The spleen hyaloserositis was significantly reduced in the combination treatment of 5-FU and KK4-PSE. These results suggest that KK4-PSE has the potential to limit cervical cancer cell proliferation while reducing the toxicity of cisplatin and 5-FU.