Cytotoxic effects of curcumin in osteosarcoma cells

Dear editor

We read with interest the results of the study from Chang et al¹ in the International Journal of Nanomedicine. This article shows that curcumin (diferuloymethane), a phenolic compound extracted from the natural plant Curcuma longa L., exerts higher cytotoxicity in osteosarcoma MG-63 cells than in healthy human osteoblasts. Based on the dosages provided by the authors it is hypothesized that with the appropriate drug carriers, curcumin could be delivered to bone tumors and selectively kill osteosarcoma cells without harming healthy osteoblasts. This hypothesis is based in the data provided that claims the dose needed to exert a significant cytotoxicity on osteosarcoma cells was much lower than that needed to exert the same effect on healthy human osteoblasts. The topic of this study is of importance for both cancer and metabolic bone disease fields, we appreciate the methodology of the study, nevertheless we believe that the hypothesis formulated by the authors and their conclusion deserves further comment.

Closer examination of the data raises some concerns regarding the study as the results presented are not in agreement with several previous studies using MG-63 cells and curcumin. Chang et al¹ presents significant cytotoxicity after MG-63 cell exposure to 5 μM curcumin, increased cytotoxicity with 10 μM, and the highest level of cytotoxicity (less than the 12% of viability in the cultures) after 24 hours of exposure to 25–100 μM. Our attention was drawn to the apparent high cytotoxicity of low concentrations of the polyphenol curcumin observed by the authors in the MG-63 cell line-based experiments. Initially, these results appeared to be markedly different from observations made in several laboratories where concentrations of curcumin had lower cytotoxic effects.

In 2008 Walters et al² reported an IC₅₀ for curcumin after 72 hours of exposure of 19.1 μM, which was slightly lower than that reported in 2012 by Li et al³ of 22.77±1.70 μM (also after 72 hours of exposure). In this last study,³ significant cytotoxicity was also reported after 24 hours (similar to the methodology reported by Chang et al) only with dosages over 22.5 μM of curcumin. Our group have also reported significant cytotoxicity after MG-63 cell exposure, but only with doses over 20 μM after 24 hours.⁴ More recently, and closer to the Chang et al hypothesis, curcumin has been encapsulated in liposomal nanoparticles and has reported to have an IC₅₀ of 23.39 μM after 48 hours of exposure of MG-63 cells.⁵

In conclusion, we wish to thank the authors for bringing this apparent lower toxicity of curcumin in healthy osteoblasts to our attention. However, their observations are not in agreement with the literature on MG-63 cells. Clearly further studies are required in this area to establish the optimal physiological concentration at which curcumin may exert cytotoxic effects on osteosarcoma cells without cytotoxic sequelae over healthy osteoblasts. In addition it would be beneficial to compare the effects of curcumin on osteosarcoma cell viability across a number of different cell lines.