[Background/Aims] We evaluated the direct cytotoxic effects and toxicity of a dried powder sample derived from Japanese Kyoho grapes. This sample utilized a digestive and absorption treatment process designed for oral administration, without extraction or concentration. The sample rapidly and synchronously broke seed dormancy and promoted phase transitions in its constituents. We assessed the effects on human pancreatic cancer, breast cancer, and liver cancer cells, as well as on fibroblasts as normal cells. Furthermore, we investigated the immune-activating effects using human natural killer cells. Evaluation methods employed a novel, proprietary 1h phenotypic screening method—high-precision surface plasmon resonance (HP-SPR-3D)—used as an in vivo-like drug sensitivity test, along with cell assays.

[Results] For all cancers, concentration-dependent efficacy was observed, with effects noted at 2.5 mg/ml or higher and maximum efficacy at 5.0 mg/ml. Higher concentrations exhibited toxicity consistent with mitochondria shutdown, distinct from typical necrosis. In pancreatic cancer, efficacy equivalent to or exceeding that of doxorubicin, paclitaxel, and gemcitabine was achieved despite oral administration. Immune activation was observed from at least 3.75 mg/ml up to 5.0 mg/ml. At these concentrations, normal cells showed almost no effect. These findings indicate that the anti-cancer effects of rapidly and synchronously dormancy-breaking Kyoho grape seed endosperm result from both direct cancer cell killing and indirect immune-mediated effects, both occurring at the same physiologically active concentration. Based on the above, it is anticipated that synergistic effects, such as those achieved by combining two types of anti-cancer drugs, can be obtained simultaneously without side effects.