Salvianolic Acid B Induces Apoptosis in Human Glioma U87 Cells Through p38-Mediated ROS Generation

Wang, Zi-shu; Luo, Peng; Dai, Shuhui; Liu, Zao-bin; Zheng, Xianfeng; Chen, Tao

doi:10.1007/s10571-013-9958-z

Cited by 52 publications

(48 citation statements)

References 24 publications

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“…[38][39][40][41] However, some studies demonstrated contrary views. [42][43][44] The different regulation networks may cause varied biological effects in diverse cells and organisms. To elucidate the specific relationship between ROS and p38, we checked the effect of NAC and SB202190, selective inhibitors of ROS and p38, respectively.…”

Section: Discussionmentioning

confidence: 99%

Danshensu Inhibits β-Adrenergic Receptors-Mediated Cardiac Fibrosis by ROS/p38 MAPK Axis

Tian

et al. 2014

Biological & Pharmaceutical Bulletin

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Danshensu, the effective ingredient of the plant Salvia miltiorrhiza (Danshen), has been widely used for treatment of cardiovascular diseases. Cardiac fibrosis is an important process in pathological cardiac remodeling and leads to heart failure. We investigated the effect of Danshensu on β-adrenergic receptor (β-AR)-mediated cardiac fibrosis and the involved signaling transduction. Danshensu inhibited cardiofibroblast proliferation and collagen I synthesis induced by isoproterenol (ISO), a selective β-AR agonist. Phosphorylation of p38 mitogen-activated protein kinase (MAPK), which mediates ISO-induced cardiac fibrosis, was negatively regulated in this process. The negative regulation depended on the ISO inhibition of reactive oxygen species (ROS) production. Taken together, Danshensu may inhibit β-AR-mediated cardiac fibrosis by negative regulation of ROS-p38 MAPK signaling.Key words Danshensu; β-adrenergic receptor; cardiac fibrosis; p38 MAPK; reactive oxygen specy Cardiac fibrosis is a pivotal phenomenon in pathological cardiac remodeling and is a hallmark of heart diseases. It is characterized by excessive extracellular matrix accumulation and fibroblast deposition and eventually destroys the organ architecture and abolishes normal function.1-3) Myocardial fibrosis is a major biological determinant of fatal events in cardiac remodeling, including heart failure, severe arrhythmias and sudden cardiac death.4,5) Cardiac fibrosis can be caused by various factors, such as the chronic activation of the sympathetic nervous system, myocardial hypoxia, ischemia, senescence, inflammation and hormones. β-Adrenergic receptors (β-ARs) and their associated guanine nucleotide regulatory protein (G protein)/adenylyl cyclase signal transduction pathways, are central to the regulation of cardiac function. Continuous activation of β-ARs plays an important role in cardiac dysfunction.6-8) Cardiac function was altered in β 1 -AR transgenic mice with cardiac hypertrophy, which could be inhibited by β-AR blockers.8) Consecutive administration with isoproterenol (ISO), a β-AR agonist, caused cardiac fibrosis in rats. 9,10) p38 mitogen-activated protein kinase (p38 MAPK) and reactive oxygen species (ROS) play a critical role in cardiac * To whom correspondence should be addressed. e-mail: lizijian@bjmu.edu.cn;zhengxh@nwu.edu.cnThe authors declare no conflict of interest. # These authors contributed equally to this work.

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Section: Discussionmentioning

confidence: 99%

Danshensu Inhibits β-Adrenergic Receptors-Mediated Cardiac Fibrosis by ROS/p38 MAPK Axis

Tian

et al. 2014

Biological & Pharmaceutical Bulletin

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“…Conversely, extracellular signal-regulated kinase (ERK)1/2, as another transduction factor of the MAPK signaling cascade, may also promote cell proliferation and migration under certain circumstances (37). However, it has been identified that p38MAPK is more active in the process of promoting cell migration, compared with the ERK1/2 signaling cascade (38).…”

Section: Discussionmentioning

confidence: 99%

Silibinin inhibits the migration and invasion of human gastric cancer SGC7901 cells by downregulating MMP‑2 and MMP‑9 expression via the p38MAPK signaling pathway

Zhang

Chen

et al. 2017

Oncol Lett

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Abstract. The objective of the present study was to observe the effects of silibinin and the p38 mitogen-activated protein kinase (MAPK) signaling pathway inhibitor SB203580 on the migration and invasion capabilities of SGC7901 cells, and to explore the underlying associated mechanisms. Scratch, Transwell and Matrigel invasion assays were performed to study the effects of silibinin on cell migration and invasion. Western blot analysis was used to determine the expression levels of p38MAPK, phosphorylated (p-)p38MAPK, matrix metalloproteinase (MMP)-2 and MMP-9. At the genomic level, quantitative polymerase chain reaction was performed to evaluate the expression levels of MMP-2 and MMP-9. The results of scratch assay indicated that silibinin inhibited the migration capabilities of human gastric cancer SGC7901 cells in a dose-dependent manner. Additionally, Matrigel invasion and Transwell migration assays revealed that silibinin and SB203580 combined treatment significantly reduced the number of invasive cells. Western blot analysis indicated a reduced phosphorylation of p38MAPK without marked changes in p38MAPK expression. In addition, the expression of MMP-2 and MMP-9 significantly decreased in the presence of silibinin, SB203580, and the combination of silibinin and SB203580. In summary, silibinin decreased the invasion and migration abilities of SGC7901 cells by downregulating the expression of MMP-2 and MMP-9 through inhibiting p38MAPK signaling cascades.

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“…The present study observed that salvianolic acid B suppressed cell proliferation, induced apoptosis and activated cleaved caspase 3 of the osteosarcoma MG63 cell. Wang et al (12) suggested that salvianolic acid B induced apoptosis through p38-mediated ROS generation in human glioma U87 cells and suppressed the growth and angiogenic potential of oral squamous carcinoma cells (20) and neuroblastoma SH-SY5Y cell lines (16).…”

Section: Discussionmentioning

confidence: 99%

“…Water they reduce blood pressure, provide anti-thrombotic activity, expand the blood vessels, increase capillary permeability (12). Clinically, injections of Danshen may expand blood vessels, increase coronary artery blood flow and promote the recovery of ischemic or damaged myocardium, and may treat multiple types of cardiovascular disease (13).…”

Section: Introductionmentioning

confidence: 99%

Salvianolic acid B suppresses cell proliferation and induces apoptosis in osteosarcoma through p38-mediated reactive oxygen species generation

et al. 2017

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Abstract. The present study aimed to investigate the potential anticancer effect and mechanisms of salvianolic acid B on osteosarcoma. Salvianolic acid B suppressed osteosarcoma cell proliferation and induced apoptosis in the osteosarcoma MG63 cell line, and activated the expressions of cleaved caspase-3, phosphorylated-tumor protein (p)38 mitogen-activated protein kinase (p-p38 MAPK) and phosphorylated-p53 (p-p53) proteins in the MG63 cells. Additionally, Salvianolic acid B also increased the level of reactive oxygen species (ROS) generation in the MG63 cells. The silencing of p38 expression inhibited the anticancer effect of salvianolic acid B on the levels of cell proliferation, p-p53 protein expression and ROS generation level in the MG63 cells. All these data supported the hypothesis that the anticancer effect of salvianolic acid B includes the suppression of cell proliferation and induces apoptosis in MG63 cells, and that p38 is important in the anticancer effect of salvianolic acid B on osteosarcoma cells due to the direct regulation of ROS generation. These data suggest that salvianolic acid B is important in the proliferation of osteosarcoma cells due to the direct regulation of p38-mediated ROS signaling. IntroductionOsteosarcoma is a type of primary malignant tumor that exhibits the highest morbidity of all neoplasms in the human skeletal system, and often presents in the metaphysis of the long tubal bones (1). Osteosarcoma often affects young people between the age of 20 and 30 years old. The mortality rate is high (2) and ~20% of patients exhibit pulmonary metastasis prior to diagnosis. Subsequent to diagnosis, the majority of patients succumb to the disease within 2 years (2). At present, there are no effective therapeutic treatments for early osteosarcoma (3). Therefore, it is important to investigate the causes of osteosarcoma occurrence, development and invasion, the mechanisms of osteosarcoma oncogenesis, and to identify effective diagnostic and therapeutic techniques. The development of gene therapy has created novel research targets in oncotherapy, including the identification of a target gene (4).Mitogen-activated protein kinase (MAPK) is the one of the most important types of signal conduction pathway in humans, and interacts with multiple signaling pathways (5). The tumor protein (p)38 MAPK pathway is activated through phosphotyrosine and threonine and inflammatory and growth factors, and activates downstream transcription factors on target genes, increases the initiation of cancer cell development, promotes protein synthesis, regulates cell surface receptors and regulates the invasion and transfer of tumor cells (6).Reactive oxygen species (ROS) are secondary products in the process of aerobic metabolism and include oxygen ions, peroxide and oxygen radical molecules (7). The increase in the level of intracellular ROS may promote cellular proliferation and differentiation to some extent. However, excessive levels of ROS results in damage to lipids, proteins and DNA, destroying numerous nor...

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Salvianolic Acid B Induces Apoptosis in Human Glioma U87 Cells Through p38-Mediated ROS Generation

Cited by 52 publications

References 24 publications

Danshensu Inhibits β-Adrenergic Receptors-Mediated Cardiac Fibrosis by ROS/p38 MAPK Axis

Danshensu Inhibits β-Adrenergic Receptors-Mediated Cardiac Fibrosis by ROS/p38 MAPK Axis

Silibinin inhibits the migration and invasion of human gastric cancer SGC7901 cells by downregulating MMP‑2 and MMP‑9 expression via the p38MAPK signaling pathway

Salvianolic acid B suppresses cell proliferation and induces apoptosis in osteosarcoma through p38-mediated reactive oxygen species generation

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