Oxymatrine triggers apoptosis by regulating Bcl-2 family proteins and activating caspase-3/caspase-9 pathway in human leukemia HL-60 cells

Abstract

With the objective of identifying promising antitumor agents for human leukemia, we carried out to determine the anticancer ability of oxymatrine on the human leukemia HL-60 cell line. In vitro experiments demonstrated that oxymatrine reduced the proliferation of HL-60 cells in a dose- and time-dependent manner via the induction of apoptosis and cell cycle arrest at G2/M and S phases. The proteins involved in oxymatrine-induced apoptosis in HL-60 cells were also examined using Western blot. The increase in apoptosis upon treatment with oxymatrine was correlated with downregulation of anti-apoptotic Bcl-2 expression and upregulation of pro-apoptotic Bax expression. Furthermore, oxymatrine induced the activation of caspase-3 and caspase-9 and the cleavage of poly(ADP-ribose) polymerase (PARP) in HL-60 cells. In addition, pretreatment with a specific caspase-3 (Z-DEVD-FMK) or caspase-9 (Z-LEHD-FMK) inhibitor significantly neutralized the pro-apoptotic activity of oxymatrine in HL-60 cells, demonstrating the important role of caspase-3 and caspase-9 in this process. Taken together, these results indicated that oxymatrine-induced apoptosis may occur through the activation of the caspase-9/caspase-3-mediated intrinsic pathway. Therefore, oxymatrine may be a potential candidate for the treatment of human leukemia.

RETRACTED: Effects of Oxymatrine on the Proliferation and Apoptosis of Human Hepatoma Carcinoma Cells

“…6,[21][22][23] However, little is known about its effects on human hepatoma, and the precise mechanism involved remains largely unknown. Therefore, in this study, we proved the anticancer effects of oxymatrine on human hepatoma Hep-G2 and SMMC-7721 cells and explored the related molecular mechanisms.…”

“…During the process, apoptosis is characterized by cell shrinkage, chromatin condensation, blebbing of the plasma membrane, and nuclear condensation without cell lysis. 21,24 Apoptosis can be induced by a variety of physical and chemical factors and drugs. 25 Since deregulation of apoptosis is the hallmark of all cancer cells, 26 the induction of apoptosis has been described as a standard and best strategy in anticancer therapy.…”

“…[11][12][13][14][15] Recently, oxymatrine has been extensively studied for their cancer chemopreventive potential against various cancers, for instance, human pancreatic cancer, 16 gastric cancer, 17 breast cancer, 18 lung cancer, 19 osteosarcoma, 20 and leukemia. 21 However, the precise mechanisms underlying the anticancer activity of oxymatrine are largely unknown.…”

Oxymatrine inhibited cell proliferation by inducing apoptosis in human lung cancer A549 cells

“…Hence, it has become an urgent need to find a low toxicity and efficient plant extract medicine applied to the cancer treatment. Nowadays, growing evidences suggest that natural materials might be a good vehicle to anticancer [2,3]. Due to these extracts showed low toxicity and high biological activities, a lot of herb products have been used in alternative treatments of cancers [4].…”

A high-throughput direct fluorescence resonance energy transfer-based assay for analyzing apoptotic proteases using flow cytometry and fluorescence lifetime measurements

“…On the other hand, anti-apoptotic agents that mitigate neurodegeneration caused by apoptosis are known to prevent the spread of neuronal diseases [41e43]. Therefore, to establish a dynamic system to study the cellular population, we generated a FRET bioprobe for caspase-9, an upstream mediator of caspase-3 activity during apoptosis; the signal transduction properties of caspase-9 were compared with those of caspase-3 [44,45]. In this study, we also demonstrated the feasibility and future applicability of the FRET bioprobe in an apoptotic protease inhibitor/activator screening assay.…”