A novel water-soluble benzothiazole derivative BD926 triggers ROS-mediated B lymphoma cell apoptosis via mitochondrial and endoplasmic reticulum signaling pathways.
Benzothiazole derivatives are known for various biological activities, and their potency in cancer therapy have received considerable attention in recent years. However, the poor water solubility of most benzothiazole derivatives has limited their clinical application. We developed BD926, a novel water-soluble benzothiazole derivative and showed here that it could inhibit the proliferation and induce apoptosis of human Ramos B-lymphoma cells. We further showed that BD926 triggered apoptosis through both mitochondria and endoplasmic reticulum pathways. Moreover, BD926 caused cell cycle arrest at G0/G1 stage. Furthermore, accumulation of reactive oxygen species (ROS) were observed after BD926 treatment and ROS inhibitor was able to attenuate BD926-induced apoptosis, which suggested that BD926-induced apoptosis may be due to over-producing ROS. These results demonstrate the anticancer effects of BD926 in cell models and raise the possibility for the application of BD926 in cancer therapy.
College of Basic and Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China.
Min-Hui
MH
Li
School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, P.R. China.
Ping
P
Yang
Center of Science and Research, Chengdu Medical College, Chengdu, Sichuan, P.R. China.
Tai
T
Yang
School of Biomedicine Sciences, Chengdu Medical College, Chengdu, Sichuan, P.R. China.
Kun
K
Zhang
Center of Science and Research, Chengdu Medical College, Chengdu, Sichuan, P.R. China.
Yang
Y
Liu
Center of Science and Research, Chengdu Medical College, Chengdu, Sichuan, P.R. China.
Jin
J
Liu
Center of Science and Research, Chengdu Medical College, Chengdu, Sichuan, P.R. China.
Li-Mei
LM
Li
Center of Science and Research, Chengdu Medical College, Chengdu, Sichuan, P.R. China.
Xing-Yan
XY
Luo
Center of Science and Research, Chengdu Medical College, Chengdu, Sichuan, P.R. China.
Shu-Xia
SX
Yang
Center of Science and Research, Chengdu Medical College, Chengdu, Sichuan, P.R. China.
Qiang
Q
Zou
College of Basic and Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China.
Chong-Jie
CJ
Zhang
D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D052160:Benzothiazoles; D017382:Reactive Oxygen Species