Combination chemotherapy compositions and methods
a chemotherapy composition and composition technology, applied in the direction of drug compositions, biocides, antinoxious agents, etc., can solve the problems of difficult prediction of the responsiveness of a given tumour-related disease type to a particular drug, abnormal growth or cellular mass, tumour formation, etc., and achieve the effect of increasing the sensitivity of melanoma cells
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example 1
Dehydroequol-Cisplatin Synergy in vitro
[0194] The effect of a composition comprising the platinum complex cisplatin and the isoflavonoid compound dehydroequol (compound No. 12) on various cancer cell lines was assessed on culture plates. Cell viability was determined using CellTiter©. Apoptosis was evaluated using Hoechst 33342 dye.
[0195] It was found that the amount of cisplatin needed to kill a set number of cancer cells is less when in admixture with an isoflavonoid compound as compared to a control with cisplatin alone. This example demonstrates the surprising synergy between cisplatin and the isoflavonoid compounds of the present invention. Dehydroequol was found to exhibit a strong synergistic interaction with cisplatin in cell lines derived from ovarian (A2780, Cp70), prostate (DU145 and PC3) and pancreatic (HPAC) cancers. Table 1 below shows that the IC50 of cisplatin against the mentioned cell lines is markedly lowered by co-incubating representative cells with a sub-IC50...
example 2
Dehydroequol-Cisplatin, Dehydroequol-Carboplatin and Dehydroequol-Paclitaxel Synergy in vitro and in vivo
Methods
[0196] The in vitro studies were performed using ovarian cancer cells isolated from ascites using an immunomagnetic assay and established ovarian cancer cell lines CP70 and A2780. Cell viability was determined using CellTiter©. Apoptosis was evaluated using Hoechst 33342 dye. The in vivo effect was tested by injecting CP70 subcutaneously into nude mice. Animals received daily oral administration of dehydroequol, 10 or 20 mg / kg for 8 days alone or in combination with cisplatin 0.5 mg / kg. After 8 days the animals were sacrificed and the tumour volume was measured.
[0197] The IC50 for carboplatin ranged from 60 μg / ml to greater than 100 μg / ml (FIG. 1).
[0198] The IC50 for paclitaxel in the paclitaxel resistant cell line, R182, was greater than 2 μM (FIG. 2).
[0199] Pre-treatment with dehydroequol (10 μg / ml) for two hours significantly reduced the IC50 for carboplatin (0.5 ...
example 3
Toxicity—Dehydroequol and Cisplatin
[0203] No overt signs of toxicity were noted at any of the dosage regimens used as shown in FIG. 8. Fluctuations in body mass were within ethically acceptable boundaries.
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