Benzoxazole Derivative K313 Induces Cell Cycle Arrest, Apoptosis and Autophagy Blockage and Suppresses mTOR/p70S6K Pathway in Nalm-6 and Daudi Cells

Molecules

Xinwen Tang¹  Yang Liu¹  Qiang Zou¹  Pan Liu²  Maolin Wang³  Wenying Zhong³  Peilin Zhong⁴  Chunyu Zhou⁴  Enhui Li⁴  Haoxue Lv⁴ 

[1] Center of Science and Research, Chengdu Medical College, Chengdu 610513, China;College of Biological Science and Technology, Chengdu Medical College, Chengdu 610500, China;Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China;School of Pharmacy, Chengdu Medical College, Chengdu 610083, China;

关键词: k313;    b-cell acute lymphoblastic leukemia;    b-cell burkitt’s lymphoma;    cell cycle arrest;    apoptosis;    mitochondrial pathway;    autophagy blockage;   

DOI  :  10.3390/molecules25040971

来源: DOAJ

【 摘 要 】

Benzoxazole derivative K313 has previously been reported to possess anti-inflammatory effects in lipopolysaccharide-induced RAW264.7 macrophages. To date, there have been no related reports on the anticancer effects of K313. In this study, we found that K313 reduced the viability of human B-cell leukemia (Nalm-6) and lymphoma (Daudi) cells in a dose-dependent manner without affecting healthy peripheral blood mononuclear cells (PBMCs) and induced moderate cell cycle arrest at the G0/G1 phase. Meanwhile, K313 mediated cell apoptosis, which was accompanied by the activation of caspase-9, caspase-3, and poly ADP-ribose polymerase (PARP). Furthermore, cells treated with K313 showed a significant decrease in mitochondrial membrane potential (MMP), which may have been caused by the caspase-8-mediated cleavage of Bid, as detected by Western blot analysis. We also found that K313 led to the downregulation of p-p70S6K protein, which plays an important role in cell survival and cell cycle progression. In addition, treatment of these cells with K313 blocked autophagic flux, as reflected in the accumulation of LC3-II and p62 protein levels in a dose- and time-dependent manner. In conclusion, K313 decreases cell viability without affecting normal healthy PBMCs, induces cell cycle arrest and apoptosis, reduces p-p70S6K protein levels, and mediates strong autophagy inhibition. Therefore, K313 and its derivatives could be developed as potential anticancer drugs or autophagy blockers in the future.

【 授权许可】

Unknown