MAPK signaling pathways regulate mitochondrial-mediated apoptosis induced by isoorientin in human hepatoblastoma cancer cells

Li, Yuan; Wang, Jing; Xiao, Haifang; Wu, Wanqiang; Wang, Yutang; Liu, Xuebo

doi:10.1016/j.fct.2012.11.048

Cited by 95 publications

(62 citation statements)

References 59 publications

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“…Since it has been demonstrated that MAPKs and PI3K/Akt signaling pathways can mediate cell survival[29, 33–36], we examined changes in signaling proteins in these two pathways. Although both signaling pathways were activated by small-magnitude mechanical stress, phosphorylation of Akt and ERK significantly decreased, while phosphorylation of JNK and p38 MAPK increased when large-magnitude mechanical stress was loaded.…”

Section: Discussionmentioning

confidence: 99%

Cyclic Compressive Stress Regulates Apoptosis in Rat Osteoblasts: Involvement of PI3K/Akt and JNK MAPK Signaling Pathways

et al. 2016

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It is widely accepted that physiological mechanical stimulation suppresses apoptosis and induces synthesis of extracellular matrix by osteoblasts; however, the effect of stress overloading on osteoblasts has not been fully illustrated. In the present study, we investigated the effect of cyclic compressive stress on rat osteoblasts apoptosis, using a novel liquid drop method to generate mechanical stress on osteoblast monolayers. After treatment with different levels of mechanical stress, apoptosis of osteoblasts and activations of mitogen-activated protein kinases (MAPKs) and PI3-kinase (PI3K)/Akt signaling pathways were investigated. Osteoblasts apoptosis was observed after treated with specific inhibitors prior to mechanical stimulation. Protein levels of Bax/Bcl-2/caspase-3 signaling were determined using western blot with or without inhibitors of PI3K/Akt and phosphorylation of c-jun N-terminal kinase (JNK) MAPK. Results showed that mechanical stimulation led to osteoblasts apoptosis in a dose-dependent manner and a remarkable activation of MAPKs and PI3K/Akt signaling pathways. Activation of PI3K/Akt protected against apoptosis, whereas JNK MAPK increased apoptosis via regulation of Bax/Bcl-2/caspase-3 activation. In summary, the PI3K/Akt and JNK MAPK signaling pathways played opposing roles in osteoblasts apoptosis, resulting in inhibition of apoptosis upon small-magnitude stress and increased apoptosis upon large-magnitude stress.

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Section: Discussionmentioning

confidence: 99%

Cyclic Compressive Stress Regulates Apoptosis in Rat Osteoblasts: Involvement of PI3K/Akt and JNK MAPK Signaling Pathways

et al. 2016

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“…In addition, isoorientin has been shown to inhibit TNF-α-mediated production of IL-6, IL-8, and VEGF in human HaCaT cells and to suppress cell migration in 3T3 murine fibroblasts50. Moreover, isoorientin has been reported to induce apoptosis in HepG2 cells through mitochondrial damage by inhibiting PI3K/Akt/ERK signaling and activating p38/JNK signaling51. These results suggest that these compounds in ELH may contribute to its anti-cancer properties, including suppression of metastasis, angiogenesis, and tumor growth in HT1080 cells.…”

Section: Discussionmentioning

confidence: 99%

Ethanol extract of Lophatheri Herba exhibits anti-cancer activity in human cancer cells by suppression of metastatic and angiogenic potential

Kim

et al. 2016

Sci Rep

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Lophatheri Herba (LH), dried leaf of Lophatherum gracile Brongn, has long been used to reduce thirst and treat fever and inflammation in Chinese medicine. Recent studies have shown that LH has anti-viral, anti-bacterial, anti-cancer, anti-oxidant, diuretic, and hyperglycemic properties. However, the effects of an ethanol extract of L. herba (ELH), at non-cytotoxic doses, on the metastatic and angiogenic abilities of malignant tumor cells have not been reported. We found that ELH significantly suppressed p38, JNK, and NF-κB activation and proteolytic activities under phorbol 12-myristate 13-acetate (PMA) stimulation, thus leading to a decrease in metastatic potential, including migration and invasion. In addition, ELH suppressed tumor-induced angiogenesis, including migration and tube formation in human umbilical vein endothelial cells (HUVECs) and microvessel sprouting from aortic rings via decreasing the pro-angiogenic factors in tumors. Interestingly, in ovo xenografts ELH-treated HT1080 cells did not increase in volume and eventually disappeared, owing to a lack of angiogenesis. Daily oral administration of ELH at 50 and 100 mg/kg markedly inhibited metastatic colonization of B16F10 cells in the lungs of C57BL/6J mice and caused no apparent side effects. These data collectively indicate that ELH is safe and may be useful for managing metastasis and growth of malignant cancers.

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“…MAPK pathways involve the extracellular signal-regulated kinases: ERK1/2, c-Jun amino-terminal kinase JNK and p38 kinase (24). Recent data suggest that MAPKs may mediate apoptotic signaling induced by anticancer drugs (25).…”

Section: A B Discussionmentioning

confidence: 99%

IL-33-induced JNK pathway activation confers gastric cancer chemotherapy resistance

Ye¹,

Zhao²,

Weng³

et al. 2015

Oncology Reports

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Abstract. Inflammation is regarded as one of the major hallmarks of tumors, and has a very close relationship with gastric cancer. Interleukin-33 (IL-33), a new member of the IL-1 family, plays an important role in both inflammatory disease and tumors. The present study was designed to explore the effects of IL-33 on the proliferation, drug sensitivity, and the invasiveness of gastric cancer cells in vitro. IL-33 at concentrations lower than 100 pg/ml did not alter the inhibitory rate of gastric cancer cells. Moreover, IL-33 at these low concentrations protected against platinum-induced apoptosis in various gastric cancer cell lines, yet not in normal gastric epithelial cells. We also found that IL-33 increased the activation of the JNK pathway, and enhanced the expression of ST2. Furthermore, SP600125, a selective inhibitor of the JNK pathway, significantly blocked the protective effects of IL-33 in gastric cancer cells. In addition, Matrigel invasion assay showed that IL-33 markedly promoted gastric cancer cell invasion. In conclusion, the present study demonstrated that IL-33 protected against platinum-induced apoptosis and promoted cell invasion via activation of the JNK pathway in gastric cancer cells. In light of the prevalence of platinumbased chemotherapeutics in the treatment of gastric cancer, our results suggest that the level of IL-33 should be monitored during the treatment of gastric cancer, particularly when using platinum-based chemotherapeutics. IntroductionGastric cancer is one of the most common types of cancers. Over 1.6 million individuals succumb to gastric cancer each year in China. The Chinese incidence of gastric cancer accounts for more than 40% of the worldwide occurrences. Moreover, the progression-free survival and overall survival rates of gastric cancer patients in China are much lower than those in Europe and the US. Therefore, research concerning the characteristics and pathogenesis of gastric cancer in Chinese patients is urgently needed.Gastric cancer can be influenced by a wide range of genetic and environmental factors. A clear association has been reported between gastric cancer and chronic inflammation (1-3). Pro-inflammatory factors, including interleukin-1 (IL-1), IL-6 and tumor necrosis factor (TNF), may not only play roles in inflammation-associated carcinogenesis (4), but may also influence the chemotherapeutic sensitivity during gastric cancer treatment (5,6). IL-33 (previously known as NF-HEV), an 18-kDa protein, is a new member of the IL-1 family (7). Traditionally, the IL-1 family is well known for their effects on host defense, immune regulation and inflammation (7). However, recent research suggests that the IL-1 family is also involved in cancer development. For example IL-18, another member of the IL-1 family, acts as a pleiotropic cytokine in many types of cancer cells, and influences the invasion of gastric cancer cells under hypoxia (8). A high level of IL-18 in serum has been intensively associated with a wide variety of tumors, such as hepatocellular (9) a...

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MAPK signaling pathways regulate mitochondrial-mediated apoptosis induced by isoorientin in human hepatoblastoma cancer cells

Cited by 95 publications

References 59 publications

Cyclic Compressive Stress Regulates Apoptosis in Rat Osteoblasts: Involvement of PI3K/Akt and JNK MAPK Signaling Pathways

Cyclic Compressive Stress Regulates Apoptosis in Rat Osteoblasts: Involvement of PI3K/Akt and JNK MAPK Signaling Pathways

Ethanol extract of Lophatheri Herba exhibits anti-cancer activity in human cancer cells by suppression of metastatic and angiogenic potential

IL-33-induced JNK pathway activation confers gastric cancer chemotherapy resistance

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