The effect of Gö6976 on chronic myeloid leukemia in vitro and in vivo

ABSTRACT

Objectives

Chronic myeloid leukemia (CML) is a malignant tumor of the blood system. Gö6976, as a type of indolocarbazole and shows strong antitumor effects, but there have been no reports on the effect of Gö6976 on CML. The objectives of this research were: (1) to explore the impact of Gö6976 on CML in vitro and in vivo; and (2) to explore the drug toxicity of Gö6976 to normal cells and animals.

Methods

K562 cells and CML mice were used to explore the effect of Gö6976 on CML. Peripheral blood mononuclear cells (PBMCs), CD34+ cells, and healthy mice were used to explore the drug toxicity of Gö6976.

Results

Cell experiments showed that Gö6976 could inhibit the proliferation of K562 cells and enhance the inhibitory effects of imatinib at 5 μM and 10 μM, but it had little effect on CD34+ cells or PBMCs at concentrations less than 5 μM. Animal experiments showed that 2.5 mg/kg Gö6976 could effectively inhibit the development of CML in mice, and it had almost no effects on healthy mice at 2.5 mg/kg and 10 mg/kg.

Discussion

Because of the direct inhibitory effect of Gö6976 on CML and its pharmacological enhancement effect on imatinib, it is foreseeable that Gö6976 could become a new type of anti-CML medicine. And the further research is needed.

Conclusion

Our findings verified that Gö6976 could effectively inhibit CML in vitro and in vivo, and it is almost nontoxic to hematopoietic cells, immune cells, and healthy mice.

KEYWORDS:

• Gö6976
• chronic myeloid leukemia
• K562
• toxicity

Subject classification codes::

• 320.2430
• 310.4710

Acknowledgments

This work was supported by the [Science and Technology Research Program of Chongqing Municipal Education Commission] under Grant [No. KJ1600225]. This research was conducted under the guidance of Professor Zhimin Lu from Zhejiang Provincial Key Laboratory of Pancreatic Disease, China. Prof. Lu owns Gö6976 related patents and has given us tremendous technical support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the [Science and Technology Research Program of Chongqing Municipal Education Commission] under Grant [No. KJ1600225]. This research was conducted under the guidance of Professor Zhimin Lu from Institute of Translational Medicine, Zhejiang University, China. Prof. Lu owns Gö6976 related patents and has given us tremendous technical support.