Biological extraction of realgar by Acidithiobacillus ferrooxidans and its in vitro and in vivo antitumor activities

Abstract

Acidithiobacillus ferrooxidans is a Gram-negative, chemolithoautotrophic bacterium involved in metal bioleaching. It is used for the extraction of coarse medical realgar, which is converted into an aqueous solution. To prove its feasibility as an anticancer drug candidate, extracted realgar (ER/Af) was evaluated for its antitumor activities both in vitro and in vivo. In cytotoxicity tests, ER/Af displayed significant inhibition on cell proliferation of HepG2, SMMC7721, and H22 cells in a time and dose dependent manner. Remarkable tumor growth inhibition and survival time prolongation effects, along with no obvious toxicity, were observed in antitumor experiments against H22 cell-bearing mice. Apoptosis induction was also confirmed as one of the mechanisms involved in the efficacy of ER/Af both in vitro and in vivo. The most important observation is that ER/Af showed high selective affinity to tumor tissues with about eight-fold higher arsenic accumulations at the tumor site of mice than those of the arsenic trioxide (ATO)-treated group at the same dose (57.8 ± 3.34 μg/g dry tissue vs. 7.6 ± 0.88 μg/g dry tissue). In conclusion, A. ferrooxidans could be successfully used for the extraction of realgar and ER/Af was proved to be a promising anticancer drug candidate, which is valuable for further study and clinical trials.

Keywords::

• Acidithiobacillus ferrooxidans
• antitumor
• apoptosis
• bioleaching
• extraction
• realgar

Declaration of interest: This work was funded by the Science and Technology Program of Gansu Province (Grant Nos. 2GS035-A52-008-01, 2GS064-A43-019-02), Science Foundation of the Ministry of Education (Grant No. 107108), and the International Cooperative Program of Gansu Province (Grant No. 0708WCGA150) in P. R. China.