Inhibition of Human Breast Carcinoma Cell Proliferation by Ascorbate and Copper

MJ González¹, EM Mora², JR Miranda Massari ³ and J Matta⁴ RECNAC II Project, School of Public Health¹, School of Medicine², School of Pharmacy³, Medical Sciences Campus⁴, UPR and Ponce School of Medicine⁵

Effective treatment of solid tumors and their metastasis has been elusive, inconsistent and extremely toxic.  Moreover, in the last two decades different combination protocols have not changed disease free survival and total survival.  We are studying a different form of therapy based on a nontoxic  metabolic approach.  

This innovative model consists on changing the cellular environment as a mean of controlling malignant cell growth.  We tested the effect of different concentrations of ascorbate (50, 100, 250, 500 mg/dL) and copper sulfate (10 mcg/dL) on human breast carcinoma cell proliferation in-vitro.  Cell proliferation was measured using a  colorimetric assay (Cell Proliferation Kit II XTT, Boehringer Mannheim) 

The results of the mean absorbance of the tissue culture at different ascorbate concentrations and a constant copper concentration were as follow: 0.82 ±0.03 SE (control), 0.64 ± 0.02 SE (Cu alone), 0.48 ± 0.03 SE (50 mg/dL of ascorbate), 0.21 ± 0.02 SE (100 mg/dL), 0.08 ± 0.01 SE, 0.60 ± 0.05 SE.  

These preliminary results show that a combination of ascorbate and copper inhibits human breast carcinoma cell proliferation in vitro. This cell proliferation inhibitory effect is directly proportional to the ascorbate concentration.  This synergistic chemotherapeutic effect was optimally enhanced when ascorbate was added at a concentration of 250 mg/dL. The ascorbate concentration of 500 mg/dL had a biphasic  effect on tumor cell proliferation.

This study provides preliminary evidence that ascorbate and copper can be use as biological response modifiers of tumor growth, thus a potential conceivableuse as chemotherapeutic agents.