M. Waheed Roomi, Aleksandra Niedzwiecki, Matthias Rath. Dr. Rath Research Institute, Santa Clara, CA
Presented at: 107th Annual Meeting of the American Association for Cancer Research, New Orleans, LA, April 16-20, 2016.
Published in: Proceedings of the 107th Annual Meeting of the AACR, vol 57, Abstract #4053, page 1039.
Ovarian cancer is the deadliest gynecological malignancy in women, and fifth leading cause of death. The American Cancer Society estimated that it would claim 14,250 lives in 2013. Despite the advances made in chemotherapy and surgery, the average time of clinical remission is approximately 2 years and the 5-year survival rate is 45%. Thus, there is an urgent need for the development of a novel therapeutic approach to ovarian cancer treatment. We investigated the effect of a unique nutrient mixture (EPQ) containing ascorbic acid, lysine, proline, green tea extract and quercetin on human ovarian cancer cell A-2780 in vivo and in vitro. Athymic female nude mice (n=12) were inoculated by I.P. with 2x106 cells in 0.1ml PBS and randomly divided into two groups. Group A (n=6) was fed a regular diet and group B (n=6) a regular diet supplemented with 0.5% EPQ. Four weeks later, the mice were sacrificed and tumors that developed in the ovary were excised, weighed and processed for histology. In vitro, A-2780 cells were cultured in Dulbecco modified Eagle medium supplemented with 10% FBS and antibiotics. At near confluence, cells were treated with EPQ in triplicate at concentrations between 0-1000 μg/ml. Cell proliferation was measured by MTT assay, MMP-9 secretion by gelatinase zymography, invasion through Matrigel and morphology by H&E staining. All control mice developed large ovarian tumors, whereas 5 out of 6 mice in the EPQ group developed no tumors, and one, a small tumor. EPQ suppressed tumor growth by 87% (p<0.0001). Lung metastasis was noted in 6 out of 6 mice in the control group, whereas no metastasis was observed in the EPQ group of mice. Zymography demonstrated only MMP-9 expression, which EPQ inhibited in a dose dependent fashion, with virtual total block at 250 μg/ml concentration. EPQ significantly inhibited invasion through Matrigel with total block at 250 μg/ml concentration. MTT showed dose dependent inhibition of cell proliferation with EPQ with 80% at EPQ 1000 μg/ml and H&E staining showed no morphological changes below 500 μg/ml EPQ. These results suggest that EPQ has therapeutic potential in treatment of ovarian cancer by significantly suppressing tumor growth and by inhibiting MMP-9 secretion and invasion of A-2780 ovarian cancer cells.
Despite advances in standard treatment of ovarian cancer, it remains the deadliest gynecological malignancy in women, with a 5-year survival rate of only 45%. We investigated the effect of a unique nutrient mixture (EPQ) containing ascorbic acid, lysine, proline, green tea extract and quercetin on human ovarian cancer cell A-2780 in vivo and in vitro. Athymic female nude mice were inoculated by I.P. with 2x106 cells and randomly divided into two groups; the control group (n=6) was fed a regular diet and the EPQ (n=6) group a regular diet supplemented with 0.5% NM. EPQ significantly suppressed ovarian tumor incidence by 83% and tumor growth by 87% (p<0.0001) and completely prevented lung metastasis. The profound reduction in tumor growth and metastasis was supported by the in vitro results; EPQ inhibited A-2780 cellular secretion of MMP-9 and Matrigel invasion with total block at 250 μg/ml. In addition cell proliferation was inhibited with 80% at EPQ 1000 μg/ml. The results indicate that EPQ has therapeutic potential in treatment of ovarian cancer