Study of cytotoxicity of complex of poly-γ-glutamic acid from Bacillus l. and doxorubicin in tumor cell lines

Introduction: The development of carrier-antitumor complexes is aimed at reducing toxicity to normal cells and increasing antitumor activity. The aim of this paper was to study the antioxidant activity and cytotoxicity of the complex of poly-γ-glutamic acid - Doxorubicin in different ratios on different cultures of tumor cells in comparison with the toxicity of Doxorubicin alone

Methodology: Poly-γ-glutamic acid (PGA) is anionic biopolymer produced by Bacillus licheniformis M 20G. Antioxidant activity was determined by DPPH-test. Cell lines were A549, LL, P3HR1, MDBK. Cytotoxicity was measured by MTT.

Results: PGA-Dox complexes showed antioxidant activity up to 25%. It was shown that in cell cultures of tumor cells A549 complex showed greater toxicity after 48 hours compared with Doxorubicin more than 2 times, the CC₅₀ for Doxorubicin was 1.5 µg/ml, and for the PGA-Dox complexes - 0.31 - 0.72 µg/ml. In P3HR1 cells the CC₅₀ for Doxorubicin was 0.68 µg/ml and in the PGA-Dox complex 0.31 - 0.68 µg/ml. In Lewis carcinoma cells (LL), the complexes were more effective after 24 h (the CC₅₀ were 0.92 - 1.06 µg/ml for PGA-Dox, 1.14 µg/ml for Dox). For non-tumor cells of MDBK Doxorubicin was as toxic as for tumor cells (CC₅₀ was 1.24 µg/ml), and the toxicity of the PGA-Dox complexes were significantly lower (3.38-68.4 µg/ml).

Conclusion: The results presented in this work demonstrated that the PGA-Dox complexes exhibited greater toxicity to tumor cells than Doxorubicin and were less toxic to cells of non-tumor origin.