Osthole Exhibits Anti-Cancer Property in Rat Glioma Cells Through Inhibiting PI3K/Akt and MAPK Signaling Pathways

Ding, Daofang; Wei, Song-Pu; Song, Yi; Li, Linghui; Du, Guoqing; Zhan, Hongsheng; Cao, Yuelong

doi:10.1159/000356609

Cited by 44 publications

(33 citation statements)

References 35 publications

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“…Researchers try to enhance anti-lung cancer activity of curcumin via catanionic lipid nanosystems [8]. Several reports have demonstrated that osthole inhibited cell growth and proliferation by inducing apoptosis, cell cycle arrest, and inhibition of migration and invasion in various types of tumors, such as glioma, colorectal cancer, and lung cancer [14,30,31,32]. Our experiment demonstrated that osthole inhibits MG-63 and SAOS-2 cells growth by at least partially inducing cell cycle arrest and inhibition of migration and invasion, suggesting that osthole could be used for the treatment of osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Osthole Induces Cell Cycle Arrest and Inhibits Migration and Invasion via PTEN/Akt Pathways in Osteosarcoma

Wang

Lei

et al. 2016

Cell Physiol Biochem

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Background/Aims: Osteosarcoma is the second highest cause of cancer-related death in children and adolescents. Majority of osteosarcoma patients (90%) show metastasis. Previous reports revealed that osthole showed antitumor activities via induction of apoptosis and inhibition of proliferation. However, the potential effects and detailed molecular mechanisms involved remained unclear. Methods: Cell viability was analyzed by MTT assay in osteosarcoma cell lines MG-63 and SAOS-2. Cell cycle was detected by flow cytometry. The effects of migration and invasion were evaluated by wound healing assay and transwell assays. Moreover, the level of proteins expression was determined by Western blot. Results: The cell viability of MG63 and SAOS-2 were markedly inhibited by osthole in a dose- and time-dependent manner. Cell cycle was arrested and the ability of migration and invasion was obviously reduced when cells were exposed to osthole. Moreover, enzymes involved in PTEN/Akt pathway were regulated such as PTEN and p-Akt proteins. Furthermore, osthole inhibited the tumor growth in vivo. Conclusion: Our study unraveled, for the first time, the ability of osthole to suppress osteosarcoma and elucidated the regulation of PTEN/Akt pathway as a signaling mechanism for the anti-tumor action of osthole. These findings indicate that osthole may represent a novel therapeutic strategy in the treatment of osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Osthole Induces Cell Cycle Arrest and Inhibits Migration and Invasion via PTEN/Akt Pathways in Osteosarcoma

Wang

Lei

et al. 2016

Cell Physiol Biochem

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“…Several studies have suggested that Akt, p38, JNK, and ERK1/2 cascades have critical roles in the induction of apoptosis [30,31]. Therefore, to elucidate the mechanisms underlying IUA-induced apoptosis, the levels of Akt, p-Akt, p38, p-p38, JNK, p-JNK, ERK1/2, and p-ERK1/2 were analyzed by Western blotting in osteosarcoma cells.…”

Section: Discussionmentioning

confidence: 99%

A New Synthetic Ursolic Acid Derivative IUA with Anti-Tumor Efficacy Against Osteosarcoma Cells via Inhibition of JNK Signaling Pathway

Chen

Wang

et al. 2014

Cell Physiol Biochem

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Background: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and is characterized by frequent metastasis and resistance to chemotherapy. Because osteosarcoma cells are not highly susceptible to current chemotherapy drugs, new alternative strategies for the treatment of osteosarcoma are needed. This study was undertaken to investigate the inhibitory effects of a new synthetic ursolic acid derivative IUA on osteosarcoma cells and to explore its molecular mechanism. We also intended to identify new therapeutic candidates. Methods: We used MTT assay to assess the effect of IUA on the proliferation of osteosarcoma cells. Western-blot analysis was performed to examine downstream molecular events. The Annexin V method was used to evaluate the effect of IUA on apoptosis of osteosarcoma cells. The cell cycle of IUA-treated cells was examined by flow cytometry, and the in vivo effects of this new ursolic acid derivative were evaluated in a mouse osteosarcoma model. Results: The results showed that the new synthetic ursolic acid derivative IUA significantly decreased viability of osteosarcoma cells in vitro and in vivo. It could also induce apoptosis and G1 phase arrest of osteosarcoma cells. The JNK signaling pathway was significantly inhibited, and cleaved caspase-3 protein was increased. Conclusion: We concluded that the new synthetic ursolic acid derivative IUA induces proliferation inhibition and apoptosis of osteosarcoma cells in vitro and in vivo via the down-regulation of the JNK signaling pathway, making it a promising agent for the prevention and treatment of human osteosarcoma.

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“…The most studied MAPKs are the p38 MAPK, extracellular signal-regulated protein kinases 1/2 (ERK1/2) and c-Jun N-terminal kinases (JNK) (6). It has been reported that p38 MAPK and ERK1/2 pathways are important for glioma development (10)(11)(12). Previous studies have demonstrated that MAPKs (p38 MAPK and ERK1/2) also activate other signaling cascades, such as cyclooxygenase-2 (COX-2) (13,14), in a variety of cancer cell types.…”

Section: Introductionmentioning

confidence: 99%

Exogenous hydrogen sulfide promotes C6 glioma cell growth through activation of the p38 MAPK/ERK1/2-COX-2 pathways

et al. 2015

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Abstract. Hydrogen sulfide (H 2 S) participates in multifarious physiological and pathophysiologic progresses of cancer both in vitro and in vivo.We have previously demonstrated that exogenous H 2 S promoted liver cancer cells proliferation/anti-apoptosis/angiogenesis/migration effects via amplifying the activation of NF-κB pathway. However, the effects of H 2 S on cancer cell proliferation and apoptosis are controversial and remain unclear in C6 glioma cells. The present study investigated the effects of exogenous H 2 S on cancer cells growth via activating p38 MAPK/ERK1/2-COX-2 pathways in C6 glioma cells. C6 glioma cells were treated with 400 µmol/l NaHS (a donor of H 2 S) for 24 h. The expression levels of phosphorylated (p)-p38 MAPK, total (t)-p38 MAPK, p-ERK1/2, t-ERK1/2, cyclooxygenase-2 (COX-2) and caspase-3 were measured by western blotting assay. Cell viability was detected by Cell Counting . Apoptotic cells were observed by Hoechst 33258 staining assay. Cell proliferation was directly detected under fully automatic inverted microscope. Exposure of C6 glioma cells to NaHS resulted in cell proliferation, as evidenced by an increase in cell viability. In addition, NaHS treatment reduced apoptosis, as indicated by the decreased apoptotic percentage and the cleaved caspase-3 expression. Importantly, exposure of the cells to NaHS increased the expression levels of p-p38 MAPK, p-ERK1/2 and COX-2. Notably, co-treatment of C6 glioma cells with 400 µmol/l NaHS and AOAA (an inhibitor of CBS) largely suppressed the above NaHS-induced effects. Combined treatment with NaHS and SB203580 (an inhibitor of p38 MAPK) or PD-98059 (an inhibitor of ERK1/2) resulted in the synergistic reduction of COX-2 expression and increase of caspase-3 expression, a decreased number of apoptotic cells, along with decreased cell viability. Combined treatment with NS-398 (an inhibitor of COX-2) and NaHS also resulted in the synergistic increase of caspase-3, a decreased in the number of apoptotic cells and the decrease in cell viability. The findings of the present study provide novel evidence that p38 MAPK/ERK1/2-COX-2 pathways are involved in NaHS-induced cancer cell proliferation and anti-apoptosis in C6 glioma cells.

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Osthole Exhibits Anti-Cancer Property in Rat Glioma Cells Through Inhibiting PI3K/Akt and MAPK Signaling Pathways

Cited by 44 publications

References 35 publications

Osthole Induces Cell Cycle Arrest and Inhibits Migration and Invasion via PTEN/Akt Pathways in Osteosarcoma

Osthole Induces Cell Cycle Arrest and Inhibits Migration and Invasion via PTEN/Akt Pathways in Osteosarcoma

A New Synthetic Ursolic Acid Derivative IUA with Anti-Tumor Efficacy Against Osteosarcoma Cells via Inhibition of JNK Signaling Pathway

Exogenous hydrogen sulfide promotes C6 glioma cell growth through activation of the p38 MAPK/ERK1/2-COX-2 pathways

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