Details

Autor(en) / Beteiligte

• Long, Qun
• Xiao, Xiao
• Yi, Ping
• Liu, Yuancui
• Varier, Krishnapriya M.
• Rao, Qing
• Song, Jingrui
• Qiu, Jianfei
• Wang, Chunlin
• Liu, Wuling
• Gajendran, Babu
• He, Zhixu
• Liu, Sheng
• Li, Yanmei

Titel

L20, a Calothrixin B analog, induces intrinsic apoptosis on HEL cells through ROS/γ-H2AX/p38 MAPK pathway

Ist Teil von

• Biomedicine & pharmacotherapy, 2021-05, Vol.137, p.111336-111336, Article 111336

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Erythroleukemia is a malignant disease in the blood system. Quinones consists of a class of antitumor agents. Calothrixin B is a carbazole-1,4-quinone alkaloid isolated from Calothrix cyanobacteria with a unique indolo[3,2-j] phenanthridine framework. This study aimed to investigate the anti-leukemic effect of the new Calothrixin B derivative, L20, and to dig up the underlying mechanisms. Cytotoxicity analysis of L20 has revealed that it shows significant IC50 concentrations in HEL cells at low doses (1.10 ± 0.05 µM) than in K562, and KG-1a (5.46 ± 3.09, and 1.82 ± 1.08 µM respectively). The study even revealed that the L20 could induce a dose and time-dependent cellular death in HEL cells. The L20 increased expression of phospho-γ-H2A.X and phospho-p38 in HEL cells, causing DNA damage and nuclear alterations due to the G2/M phase cell cycle arrest. The HEL cells even lost the mitochondrial membrane potential (MMP) and resulted in the release of reactive oxygen species (ROS). Additionally, L20 inhibited the proliferation of HEL cells by inducing apoptosis through the mitochondrial pathway, depending on the caspase family. The study even established this may be due to the upregulation of the p-P38MAPK and downregulation of p-ERK. Pretreatment with P38/ERK inhibitors, SB203580, and U0126, decreased L20-induced apoptosis. These findings indicated that L20 induced mitochondrial mediated-apoptosis and G2/M arrest through DNA damage and modulation of p38 MAPK pathways. Thus, the study suggests L20, a chemical analog of Calothrixin B, as a novel chemotherapeutic agent against erythroleukemia. [Display omitted] •L20, a Calothrixin B analog exerts anti-leukemia activity.•L20 reduce cellular viability in HEL cells both dose and time-dependent manner.•L20 induce intrinsic apoptosis in HEL cells.•L20 inhibits MAPK/ERK pathway in HEL cells.