B Background: The use of natural product as a source of compound for therapeutictreatment is continuously being developed. During drug development process, it isimportant to recognize the effect of natural product in healthy cells so that it can beconsidered harmless nor causing any cytotoxic effect. InsP6 is a natural product thathas been reported for its anticancer role, yet the effect requires high concentrationof the agent. Therefore, histone is added to neutralize the negative charge ofphosphate in InsP6, making it more effective. However, the effect of InsP6-histonein healthy cell is still unknown. Aim: This study was conducted to investigateapoptotic effect of InsP6-histone in NIH3T3 cells using sub G1 analysis. Method:NIH3T3 cells were treated without InsP6-histone, 1-500 µM InsP6, 1-500 µg/mLhistone, the combination of 10 µM InsP6-1-500 µg/mL histone, the combination of100 µM InsP6-1-500 µg/mL histone, and 0,037% H2O2. Treated cells were labelledwith Propidium iodide, measured by flow cytometer, and analyzed with sub G1analysis to detect apoptotic cells. Results: The combination of 10 µM InsP6-1-500µg/mL histone was not cytotoxic in NIH3T3 cells, with the percentage of apoptoticcells only up to 5,20%. The combination of 100 µM InsP6-100 µg/mL was cytotoxicin NIH3T3 cells, causing the percentage of apoptotic cells increased up to 36,05%.Conclusion: Combination of 10 µM InsP6-1-500 µg/mL histone does not induceapoptosis on NIH3T3 cells. Combination of 100 µM InsP6-100 µg/mL histoneshowed cytotoxic effect on NIH3T3 cells. The combination might increase theeffectiveness of InsP6 in inducing apoptosis in healthy cells, this indicates thatfurther examination is needed for InsP6-histone.