Abstract 3194: Inhibition of breast cancer - fibroblast interaction by specific micronutrient combinations
Authors: Shanker Neha , Roomi M. Waheed , Niedzwiecki Aleksandra , Rath Matthias 
Published: August 2015

Several previous studies have indicated that the stromal tissue in tumors plays an indispensable role in promoting tumor growth and invasion. This is due to a reciprocal interaction and communication between the stromal and neoplastic components of tissues. Even in breast cancer cell invasion and metastases a key event has been shown to be the stimulation of fibroblasts by cancer cells to secrete enzymes such as MMPs to help degrade and modify the extracellular matrix.

In this study, we investigate the in vitro and in vivo effects of two micronutrient combinations - NM1 and NM2 on the inhibition of growth and invasion of human breast cancer cell line MDA-MB-231 alone or in combination with human dermal fibroblasts (NHDF). NM1 contains ascorbic acid, lysine, proline, green tea extract and quercetin while NM2 is a combination of plant extracts such as curcumin, cruciferex, green tea extract and resveratrol.

In the in vitro studies we evaluated the effect of NM1 and NM2 on several parameters such as breast cancer cell proliferation, migration and expression of matrix degrading proteases (MMPs). Treatment of NHDF with conditioned media (CM) from MDA-MB-231 cells resulted in an enhanced MMP2 enzyme expression. However, treatment with both combinations of nutrients resulted in a dose dependent reduction in the MMP2 expression to basal or lower levels. The invasion assay also showed that the invasive ability of normal fibroblasts was significantly enhanced by co-incubation with breast cancer cells in the Boyden chamber. The invasiveness was however reduced considerably upon treatment with both NM1 and NM2. A similar dose dependent inhibition in growth, invasion and migration was observed in MDA-MB-231 alone and in co-cultures.

In the in vivo study, 5-6 week old mice were orthotopically inoculated with 4×106 MDA-MB-231 cells alone (Group 1) or in combination with fibroblasts (Group 2) into the mammary pad of female nude mice. Each group (n = 18) was further divided into 3 sets based on the diet: Set A was fed a regular diet; Set B was fed a diet supplemented with NM1 and Set C was fed a diet supplemented with NM2. After 6 weeks the mice were sacrificed and the tumors were excised and processed for histology. The tumor weight was recorded and it was found that NM1 and NM2 inhibited tumor weight by 42% each in group 1 and by 41% and 55% respectively in group 2. The tumor weight decreased from 1.78±0.28g in group 1A to 1.03±0.25g in group 1B and 1.03±0.12g in group 1C. Similarly, tumor weight showed a reduction from 1.64±0.19g in group 2A to 0.97±0.17g in group 2B and 0.74±0.26g in group 2C.

The results suggest that both NM1 and NM2 have significant therapeutic potential in treatment of breast cancer, both through a direct suppressive effect on cancer cells and through an indirect effect of limiting cancer-stromal interactions by inhibiting communication between cancer cells and fibroblasts.

Citation Format: Neha Shanker, M. Waheed Roomi, Aleksandra Niedzwiecki, Matthias Rath. Inhibition of breast cancer - fibroblast interaction by specific micronutrient combinations. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3194. doi:10.1158/1538-7445.AM2015-3194