A Specific Mixture of Nutrients Suppresses Ovarian Cancer A-2780 Tumor Incidence, Growth, and Metastasis to Lungs

Nutrients. 2017 Mar 18;9(3):303. doi: 10.3390/nu9030303.


Ovarian cancer is the deadliest gynecological malignancy in women, and fifth leading cause of death. Despite 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 specific 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 all inoculated intraperitoneally (IP) with 2 × 10⁶ cells in 0.1 mL of phosphate buffered saline (PBS) and randomly divided into two groups. Upon injection, the Control group (n = 6) was fed a regular diet and the EPQ group (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. Lungs were inspected for metastasis. 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 and 1000 μg/mL. Cell proliferation was measured via MTT assay, MMP-9 secretion via gelatinase zymography, invasion through Matrigel and morphology via hematoxylin and eosin (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. Control mice also showed lung metastasis in 6 out of 6 mice, while no lung metastasis was evident in EPQ 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, and H & E staining showed no morphological changes below 500 μg/mL EPQ. These results suggest that EPQ has therapeutic potential in the treatment of ovarian cancer by significantly suppressing ovarian tumor incidence and growth and lung metastasis, and by inhibiting MMP-9 secretion and invasion of A-2780 ovarian cancer cells.

Keywords: MMPs; Matrigel invasion; metastasis; nutrients; ovarian cancer A-2780 cell line; tumor growth.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Ascorbic Acid / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dietary Supplements
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary
  • Lysine / pharmacology
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Nude
  • Micronutrients / pharmacology*
  • Neoplasm Metastasis / prevention & control*
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / prevention & control*
  • Plant Extracts / pharmacology
  • Proline / pharmacology
  • Quercetin / pharmacology
  • Tea / chemistry
  • Xenograft Model Antitumor Assays


  • Antioxidants
  • Micronutrients
  • Plant Extracts
  • Tea
  • Proline
  • Quercetin
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse
  • Lysine
  • Ascorbic Acid