The rRNA synthesis inhibitor CX-5461 may induce autophagy that inhibits anticancer drug-induced cell damage to leukemia cells

ABSTRACT

Autophagy induced in cancer cells during chemotherapy is classified into two types, which differ depending on the kind of cells or anticancer drugs. The first type of autophagy contributes to the death of cells treated with drugs. In contrast, the second type plays a crucial role in preventing anticancer drug-induced cell damages; the use of an autophagy inhibitor is considered effective in improving the efficacy of chemotherapy. Thus, it is important to determine which type of autophagy is induced during chemotherapy. Here, we showed that a novel inhibitor of RNA polymerase I, suppresses growth, induces cell cycle arrest and promotes apoptosis in leukemia cell lines. The number of apoptotic cells induced by co-treatment with CX-5461 and chloroquine, an autophagy inhibitor, increased compared with CX-5461 alone. Thus, the autophagy which may be induced by CX-5461 was the second type.

Graphical Abstract

The number of apoptotic cells induced by co-treatment with CX-5461 and CQ increased compared with CX-5461 alone.

KEYWORDS:

• Autophagy
• CX-5461
• leukemia cell
• apoptosis anticancer

Acknowledgments

We are grateful to Chikage Kawai and Masumi Itadani (Kawasaki Medical School, Japan) for technical assistance and to the Central Research Institute of Kawasaki Medical School for technical support.

Author contributions

Substantial contributions to conception and design: SO, KM. Data acquisition, data analysis, and interpretation: SO, KM, MK, AY, FK. Drafting the article or critically revising it for important intellectual content: SO, KM, MK, AY, FK.

Disclosure statement

The authors declare that they have no conflicts of interest.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study was supported in part by JSPS KAKENHI grant numbers [JP17K08637 (KM), JP18K07804 (FK), and JP19K07676 (AY)], in part by the Wesco Scientific Promotion Foundation (KM and AY), in part by the Ryobi Teien Memory Foundation (KM and AY), in part by the Okayama Health Foundation grand (SO) and in part by Research Project Grants [nos. R01S-003 (KM), H30Y-002 (SO), R01B-081 (FK), and R01B-093 (AY)] from Kawasaki Medical School.