Microindoline 581, an indole derivative from Microbacterium sp. RP581 as a novel selective antineoplastic agent to combat hepatic cancer cells: Production optimization and structural elucidation

Document Type: Research article

Authors

1 Molecular Biotechnology Laboratory, Department of Biology, Faculty of Science, Shiraz. University, Iran. Department of Pharmaceutical Chemistry, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, CCB–Centrum for Chemistry and Biomedicine, Innrain 80-82, 6020 Innsbruck, Austria.

2 Department of Pharmaceutical Chemistry, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, CCB–Centrum for Chemistry and Biomedicine, Innrain 80-82, 6020 Innsbruck, Austria.

3 Immunobiology and Stem Cell Laboratory, Department of Internal Medicine V (Hematology and Oncology), Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. Tyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, Austria.

4 Molecular Biotechnology Laboratory, Department of Biology, Faculty of Science, Shiraz University, Iran.

Abstract

Screening of bioactive compounds with potential binding affinity to DNA as one of the target molecules in fighting against cancer cells has gained the attention of many scientists. Finding such compounds in the cellular content of microorganisms, especially marine bacteria as valuable and rich natural resources, is of great importance. Microbacterium sp. RP581, as a member of Actinobacteria phylum, was isolated from the Persian Gulf coastal area and the production of the target compound was optimized using statistical methods in cheap culture ingredients. The purification of the target compound was performed by flash chromatography and preparative HPLC. Both molecular and structural analyses indicated that the compound was an indole derivate which was tentatively named as Microindoline 581. Interaction of Microindoline 581 with genomic and circular DNA revealed that this compound can cause double- strand breaks through binding to the DNA. The analysis of cellular growth and proliferation of various cancer cell lines suggested proper and specific effect Microindoline 581 towards HepG2 cells with an IC50 of 172.2 ± 1.7 µM. Additional studies on cell migration inhibition and cell-death induction indicated a concentration-dependent inhibitory effect on proliferation and induction of death of HepG2 cells. The selective action of Microindoline 581 which was isolated from the Microbacterium sp. RP581 in killing HepG2 cells might be due to its specific metabolism in those cells as a precursor.

Graphical Abstract

Microindoline 581, an indole derivative from  Microbacterium  sp. RP581 as a novel selective antineoplastic agent to combat hepatic cancer cells: Production optimization and structural elucidation

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