Protection of Luteolin-7-O-Glucoside Against Doxorubicin-Induced Injury Through PTEN/Akt and ERK Pathway in H9c2 Cells.
Luteolin-7-O-glucoside (LUTG) was isolated from the plants of Dracocephalum tanguticum Maxim. Previous research has showed that LUTG pretreatment had a significant protective effect against doxorubicin (DOX)-induced cardiotoxicity by reducing intracellular calcium overload and leakage of creatine kinase and lactate dehydrogenase. But the underlying mechanisms have not been completely elucidated. In the present study, we investigated the effects of LUTG on H9c2 cell morphology, viability, apoptosis, reactive oxygen species generation, and the mitochondrial transmembrane potentials. The expression of p-PTEN, p-Akt, p-ERK, p-mTOR, and p-GSK-3β were detected by Western blotting. Compared with DOX alone treatment group, the morphological injury and apoptosis of the cells in groups treated by DOX plus LUTG were alleviated, cell viability was increased, ROS generation was lowered remarkably, and mitochondrial depolarization was mitigated. In DOX group, the expression of p-PTEN was lower than normal group and the expression of p-Akt and p-ERK was higher than normal group. In the groups treated with LUTG (20 μM), the expression of p-PTEN was upregulated and the expression of p-Akt, p-ERK, p-mTOR, and p-GSK-3β was downregulated. These results indicated that the protective effects of LUTG against DOX-induced cardiotoxicity may be related to anti-apoptosis through PTEN/Akt and ERK pathway.
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, 250012, China.
Hong
H
Yao
Department of Oncology, Wei Fang Traditional Chinese Hospital, 666 Weizhou Road, Weifang, 261041, China.
Zhimei
Z
Shang
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, 250012, China.
Penghong
P
Wang
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, 250012, China.
Shuixian
S
Li
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, 250012, China.
Qianyun
Q
Zhang
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, 250012, China.
Huiqin
H
Tian
Department of Natural Product Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, 250012, China.
Dongmei
D
Ren
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, 250012, China. xzyhan@sdu.edu.cn.
Xiuzhen
X
Han
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D047309:Flavones / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D051381:Rats; D047311:Luteolin
D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D004317:Doxorubicin; D047309:Flavones; D005960:Glucosides; D051059:PTEN Phosphohydrolase; D051057:Proto-Oncogene Proteins c-akt; C066408:luteolin-7-glucoside; D047311:Luteolin; C487216:Pten protein, rat
Akt; Doxorubicin; ERK; Luteolin-7-O-glucoside; PTEN