Investigation of the mutagenic and genotoxic activities of LLL-3, a STAT3 inhibitor

Abstract

LLL-3, an anthracene derived compound, has been shown to be a promising therapeutic agent for the treatment of some kinds of cancer such as chronic myeloid leukemia and glioblastoma. However, no data regarding the toxic properties of this compound have yet been described in the literature. The present work aimed to investigate the mutagenic and genotoxic activities of LLL-3 using the TA97, TA98, TA100, TA102 and TA104 Salmonella/microsome strains for the Ames test and the micronucleus assay with the mouse macrophage cell line RAW 264.7. The findings showed that LLL-3, at doses of 0.001, 0.01, 0.1, 1.0 and 10.0 μg/plate, did not induce mutagenic activity in the Salmonella strains used under the conditions tested, and nor did it present genotoxicity in RAW 264.7 cells, at 10.0, 100.0 and 1000.0 μg/mL doses. Moreover, it is important to point out that the mitotic index of the cells decreased after exposure to LLL-3 under the same conditions tested, which may suggest some cytostatic effect, since this compound acts by inhibiting STAT3. Since most drugs used in the treatment of cancer present mutagenic activity as an adverse effect, these results suggest that LLL-3 is a promising drug for cancer therapy.

• STAT3
• mutagenic
• cancer
• LLL-3
• RAW 264.7

Acknowledgements

The authors are grateful to Dr Pui-Kai Li (School of Pharmacy, Ohio State University) for kindly providing the LLL-3 compound.

Declaration of interest

The authors declare there were no conflicting interests. This research was supported by the Carlos Chagas Filho Research Support Foundation of the State of Rio de Janeiro (FAPERJ) and the National Council for Scientific and Technological Development (CNPq).