Cancer treatment is a concern due to side effects, the resistance of tumor cells, and costs. Application of alternative compounds particularly delivered by nanocarriers is a paramount approach for the efficient treatment of cancer cells. Our objective was to kill ovary and breast cancer cells using nanoniosomes containing isomeldenin plus lupeol. Herein, nanoniosomes were synthesized using the thin-layer hydration method and their physical and chemical traits were assessed using scanning electron microscopy (SEM) and Dynamic Light Scattering (DLS) analysis. The dialysis bag was also used the entrapment rate and release pattern. Various concentrations of lupeol and isomeldenin were prepared for the assessment of anticancer effects against ovary and breast cancer cells (SK-OV-3, MCF-7, and 3SKBr cell lines) using the MTT assay and gene expression. The results were compared to each bioactive compound singly and free forms of them. The expression of Bax and Bcl2 genes was examined at low concentrations of each isomeldenin and lupeol (25µg mL-1) singly and in combination with gemcitabine (25µg mL-1). The size of synthesized nanoniosomes included 203.2 nm size and the entrapment rate was 72.6%. The death rate of SK-OV-3 in exposure to isomeldenin (100 µg mL-1) included 76.34% and for MCF-7 and 3SKBr cell lines included 64.66% and 62.99%, respectively. The lupeol (100µg mL-1) killing rate against SK-OV-3, MCF-7, and 3SKBr cell lines respectively included 42.36%, 40.26%, and 39.96%. The nanoniosomes containing isomeldenin killed SK-OV-3, MCF-7, and 3SKBr cell lines at 89.6%, 78.3%, and 69.6%, respectively. Moreover, nanoniosomes containing lupeol killed SK-OV-3, MCF-7, and 3SKBr cell lines at 88.9%, 79.2%, and 66.9%, respectively. The expression of the Bax gene was decreased 3.2 fold and the Bcl2 gene was increased 2.6 fold in exposure to nanoniosomes containing both gemcitabine and lupeol being significantly higher than those of control. The combination of each isomeldenin and lupeol with gemcitabine significantly increased the death of ovary and breast cancer cells in niosomal form. Herbal bioactive compounds nano-formulation is promising for cancer therapy. تفاصيل المقالة