Abstract
In this study, we describe that a novel synthesized compound, olean-28,13β-olide 2 (OLO-2), exhibits selective cytotoxic activity via inducing apoptosis in human hepatocellular carcinoma (HCC) cell lines but not normal human hepatic cells in vitro. Exposure of human HCC HepG2 cells to OLO-2 results in significant loss of mitochondrial transmembrane potential (δ. Ψm), the release of cytochrome c, the recruitment of B-cell lymphoma 2 (Bcl-2) assaciated X protein (Bax) and the downregulation of Bcl-2. The apoptosis induced by OLO-2 is associated with the activation of caspase-3/9 and the nuclear translocation of apoptosis inducing factor (AIF). Moreover, the increase of phosphorylated p38 and c-Jun N-terminal kinase (JNK) is observed. OLO-2-induced the externalization of phosphatidyl-serine (PS) and the loss of δ. Ψm are blocked by p38 inhibitor SB203580 or JNK inhibitor SP600125. In addition, OLO-2 provokes the generation of reactive oxygen species (ROS) in HepG2 cells, while the antioxidant N-acetyl cysteine (NAC) almost completely blocks OLO-2-induced apoptosis and the activation of p38 and JNK. Taken together, the present study demonstrates that OLO-2 exhibits its cytotoxic activity through intrinsic apoptosis via ROS generation and the activation of p38 and JNK. Its potential to be a candidate of anti-cancer agent is worth being further investigated.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 38-47 |
| Number of pages | 10 |
| Journal | Food and Chemical Toxicology |
| Volume | 63 |
| DOIs | |
| State | Published - 2014 |
| Externally published | Yes |
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Keywords
- Apoptosis
- Cytotoxic
- Human HCC cells
- Mitochondria
- OLO-2
ASJC Scopus subject areas
- Food Science
- Toxicology
Cite this
The activation of p38 and JNK by ROS, contribute to OLO-2-mediated intrinsic apoptosis in human hepatocellular carcinoma cells. / Zhang, Zhenzhen; Zhang, Chao; Ding, Ye; Zhao, Qian; Yang, Lifang; Ling, Jingjing; Liu, Ling; Ji, Hui; Zhang, Yihua.
In: Food and Chemical Toxicology, Vol. 63, 2014, p. 38-47.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The activation of p38 and JNK by ROS, contribute to OLO-2-mediated intrinsic apoptosis in human hepatocellular carcinoma cells
AU - Zhang, Zhenzhen
AU - Zhang, Chao
AU - Ding, Ye
AU - Zhao, Qian
AU - Yang, Lifang
AU - Ling, Jingjing
AU - Liu, Ling
AU - Ji, Hui
AU - Zhang, Yihua
PY - 2014
Y1 - 2014
N2 - In this study, we describe that a novel synthesized compound, olean-28,13β-olide 2 (OLO-2), exhibits selective cytotoxic activity via inducing apoptosis in human hepatocellular carcinoma (HCC) cell lines but not normal human hepatic cells in vitro. Exposure of human HCC HepG2 cells to OLO-2 results in significant loss of mitochondrial transmembrane potential (δ. Ψm), the release of cytochrome c, the recruitment of B-cell lymphoma 2 (Bcl-2) assaciated X protein (Bax) and the downregulation of Bcl-2. The apoptosis induced by OLO-2 is associated with the activation of caspase-3/9 and the nuclear translocation of apoptosis inducing factor (AIF). Moreover, the increase of phosphorylated p38 and c-Jun N-terminal kinase (JNK) is observed. OLO-2-induced the externalization of phosphatidyl-serine (PS) and the loss of δ. Ψm are blocked by p38 inhibitor SB203580 or JNK inhibitor SP600125. In addition, OLO-2 provokes the generation of reactive oxygen species (ROS) in HepG2 cells, while the antioxidant N-acetyl cysteine (NAC) almost completely blocks OLO-2-induced apoptosis and the activation of p38 and JNK. Taken together, the present study demonstrates that OLO-2 exhibits its cytotoxic activity through intrinsic apoptosis via ROS generation and the activation of p38 and JNK. Its potential to be a candidate of anti-cancer agent is worth being further investigated.
AB - In this study, we describe that a novel synthesized compound, olean-28,13β-olide 2 (OLO-2), exhibits selective cytotoxic activity via inducing apoptosis in human hepatocellular carcinoma (HCC) cell lines but not normal human hepatic cells in vitro. Exposure of human HCC HepG2 cells to OLO-2 results in significant loss of mitochondrial transmembrane potential (δ. Ψm), the release of cytochrome c, the recruitment of B-cell lymphoma 2 (Bcl-2) assaciated X protein (Bax) and the downregulation of Bcl-2. The apoptosis induced by OLO-2 is associated with the activation of caspase-3/9 and the nuclear translocation of apoptosis inducing factor (AIF). Moreover, the increase of phosphorylated p38 and c-Jun N-terminal kinase (JNK) is observed. OLO-2-induced the externalization of phosphatidyl-serine (PS) and the loss of δ. Ψm are blocked by p38 inhibitor SB203580 or JNK inhibitor SP600125. In addition, OLO-2 provokes the generation of reactive oxygen species (ROS) in HepG2 cells, while the antioxidant N-acetyl cysteine (NAC) almost completely blocks OLO-2-induced apoptosis and the activation of p38 and JNK. Taken together, the present study demonstrates that OLO-2 exhibits its cytotoxic activity through intrinsic apoptosis via ROS generation and the activation of p38 and JNK. Its potential to be a candidate of anti-cancer agent is worth being further investigated.
KW - Apoptosis
KW - Cytotoxic
KW - Human HCC cells
KW - Mitochondria
KW - OLO-2
UR - http://www.scopus.com/inward/record.url?scp=84888037538&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888037538&partnerID=8YFLogxK
U2 - 10.1016/j.fct.2013.10.043
DO - 10.1016/j.fct.2013.10.043
M3 - Article
VL - 63
SP - 38
EP - 47
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
SN - 0278-6915
ER -