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

• Published in: Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2020-11, Vol.84 (11), p.2319-2326
• Main Authors: Okamoto, Shuichiro, Miyano, Kei, Kajikawa, Mizuho, Yamauchi, Akira, Kuribayashi, Futoshi
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; apoptosis anticancer; Autophagy; Autophagy - drug effects; Benzothiazoles - pharmacology; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; CX-5461; Humans; Leukemia - pathology; leukemia cell; Naphthyridines - pharmacology; Protein Biosynthesis - drug effects; RNA, Ribosomal - biosynthesis
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1080/09168451.2020.1801378

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