Alternol, a natural compound, exerts an anti‐tumour effect on osteosarcoma by modulating of <scp>STAT</scp>3 and <scp>ROS</scp>/<scp>MAPK</scp> signalling pathways

Zuo, Dongqing; Zhou, Zifei; Wang, Hongsheng; Zhang, Tao; Zang, Jie; Yin, Fei; Sun, Wei; Chen, Jiepeng; Duan, Lili; Xu, Jing; Wang, Zhuoying; Wang, Chongren; Lin, Binhui; Fu, Zeze; Li, Suoyuan; Sun, Mengxiong; Hua, Yingqi; Zheng, Longpo; Cai, Zhengdong

doi:10.1111/jcmm.12957

Cited by 34 publications

(37 citation statements)

References 39 publications

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“…Natural bioactive compounds derived from traditional Chinese medicinal herbs have been widely investigated because of their antiproliferative, antiangiogenic, and antitumor effects on various diseases, as well as their safety, efficacy and immediate availability. The effects of natural compounds on the inhibition of osteosarcoma have previously been reported by our research team . For instance, we found that pectolinarigenin significantly suppressed osteosarcoma cell proliferation, induced apoptosis and inhibited migration and invasion in osteosarcoma cells .…”

Section: Discussionsupporting

confidence: 72%

“…Our team previously reported that STAT3 is a critical regulator of osteosarcoma development and progression . The effect of RA on the JNK and STAT3 signaling pathways was assessed to investigate the molecular mechanism of the antitumor activity of RA using pharmacological inhibitors and shRNA.…”

Section: Resultsmentioning

confidence: 99%

“…For instance, we found that pectolinarigenin significantly suppressed osteosarcoma cell proliferation, induced apoptosis and inhibited migration and invasion in osteosarcoma cells . Alternol, a novel compound purified from microbial fermentation products, not only inhibited osteosarcoma cell proliferation and migration and induced caspase‐dependent apoptosis and G2/M cell cycle arrest in vitro, but also suppressed tumor growth in an orthotopic tibial osteosarcoma model . In addition, our team has demonstrated that two natural compounds, toosendanin and erianin, suppress human osteosarcoma growth and metastasis .…”

Section: Discussionmentioning

confidence: 97%

“…Compared with the transient activation of STAT3 in normal cells, STAT3 remains abnormally active in tumors and promotes the induction and survival of cancer . Our previous results showed that selective inactivation of STAT3 blocks tumorigenesis in human osteosarcoma . Our most recent studies have shown that a natural compound, alternol, suppresses cell proliferation and migration and induces apoptosis and cell cycle arrest by modulating ROS‐dependent MAPK and STAT3 signaling pathways in human osteosarcoma cells .…”

Section: Introductionmentioning

confidence: 98%

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Antitumor activity of Raddeanin A is mediated by Jun amino‐terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma

et al. 2019

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Osteosarcoma is the most common primary malignant bone tumor. Raddeanin A ( RA ) is an active oleanane‐type triterpenoid saponin extracted from the traditional Chinese herb Anemone raddeana Regel that exerts antitumor activity against several cancer types. However, the effect of RA on osteosarcoma remains unclear. In the present study, we showed that RA inhibited proliferation and induced apoptosis of osteosarcoma cells in a dose‐ and time‐dependent way in vitro and in vivo. RA treatment resulted in excessive reactive oxygen species ( ROS ) generation and JNK and ERK 1/2 activation. Apoptosis induction was evaluated by the activation of caspase‐3, caspase‐8, and caspase‐9 and poly‐ADP ribose polymerase ( PARP ) cleavage. RA ‐induced cell death was significantly restored by the ROS scavenger glutathione ( GSH ), the pharmacological inhibitor of JNK SP 600125, or specific JNK knockdown by sh RNA . Additionally, signal transducer and activator of transcription 3 ( STAT 3) activation was suppressed by RA in human osteosarcoma, and this suppression was restored by GSH , SP 600125, and JNK ‐sh RNA . Further investigation showed that STAT 3 phosphorylation was increased after JNK knockdown. In a tibial xenograft tumor model, RA induced osteosarcoma apoptosis and notably inhibited tumor growth. Taken together, our results show that RA suppresses proliferation and induces apoptosis by modulating the JNK /c‐Jun and STAT 3 signaling pathways in human osteosarcoma. Therefore, RA may be a promising candidate antitumor drug for osteosarcoma intervention.

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Section: Discussionsupporting

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

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Antitumor activity of Raddeanin A is mediated by Jun amino‐terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma

et al. 2019

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“…Finally, the media were carefully removed by aspiration. Colonies were stained by crystal violet, photographed, and scored [24]. …”

Section: Methodsmentioning

confidence: 99%

Andrographolide Induces Autophagic Cell Death and Inhibits Invasion and Metastasis of Human Osteosarcoma Cells in An Autophagy-Dependent Manner

Liu

Zhang

Zou

et al. 2017

Cell Physiol Biochem

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Background/Aims: Osteosarcoma (OS) is the most common primary malignant tumor of bone tissue. Although treatment effectiveness has improved, the OS survival rate has fluctuated in recent years. Andrographolide (AG) has been reported to have antitumor activity against a variety of tumors. Our aim was to investigate the effects and potential mechanisms of AG in human osteosarcoma. Methods: Cell viability and morphological changes were assessed by MTT and live/dead assays. Apoptosis was detected using Annexin V-FITC/PI double staining, DAPI, and caspase-3 assays. Autophagy was detected with mRFP-GFP-LC3 adenovirus transfection and western blot. Cell migration and invasion were detected by wound healing assay and Transwell® experiments. Results: AG dose-dependently reduced the viability of osteosarcoma cells. No increase in apoptosis was detected in AG-treated human OS MG-63 and U-2OS cells, and the pan-caspase inhibitor z-VAD did not attenuate AG-induced cell death. However, AG induced autophagy by suppressing PI3K/Akt/mTOR and enhancing JNK signaling pathways. 3-MA and Beclin-1 siRNA could reverse the cytotoxic effects of AG. In addition, AG inhibited the invasion and metastasis of OS, and this effect could be reversed with Beclin-1 siRNA. Conclusion: AG inhibits viability and induces autophagic death in OS cells. AG-induced autophagy inhibits the invasion and metastasis of OS.

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Glycitein induces reactive oxygen species‐dependent apoptosis and G0/G1 cell cycle arrest through the MAPK/STAT3/NF‐κB pathway in human gastric cancer cells

Zang

Feng

Luo

et al. 2019

Drug Development Research

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Glycitein is an isoflavone that reportedly inhibits the proliferation of human breast cancer and prostate cancer cells. However, its anti-cancer molecular mechanisms in human gastric cancer remain to be defined. This study evaluated the antitumor effects of glycitein on human gastric cancer cells and investigated the underlying mechanisms. We used MTT assay, flow cytometry and western blotting to investigate its molecular mechanisms with focus on reactive oxygen species (ROS) production. Our results showed that glycitein had significant cytotoxic effects on human gastric cancer cells. Glycitein markedly decreased mitochondrial transmembrane potential (ΔΨm) and increased AGS cells mitochondrial-related apoptosis, and caused G0/G1 cell cycle arrest by regulating cycle-related protein. Mechanistically, accompanying ROS, glycitein can activate mitogen-activated protein kinase (MAPK) and inhibited the signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappaB (NF-κB) signaling pathways. Furthermore, the MAPK signaling pathway regulated the expression levels of STAT3 and NF-κB upon treatment with MAPK inhibitor and N-acetyl-L-cysteine (NAC). These findings suggested that glycitein induced AGS cell apoptosis and G0/G1 phase cell cycle arrest via ROS-related MAPK/STAT3/NF-κB signaling pathways. Thus, glycitein has the potential to a novel targeted therapeutic agent for human gastric cancer.

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Alternol, a natural compound, exerts an anti‐tumour effect on osteosarcoma by modulating of STAT3 and ROS/MAPK signalling pathways

Cited by 34 publications

References 39 publications

Antitumor activity of Raddeanin A is mediated by Jun amino‐terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma

Antitumor activity of Raddeanin A is mediated by Jun amino‐terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma

Andrographolide Induces Autophagic Cell Death and Inhibits Invasion and Metastasis of Human Osteosarcoma Cells in An Autophagy-Dependent Manner

Glycitein induces reactive oxygen species‐dependent apoptosis and G0/G1 cell cycle arrest through the MAPK/STAT3/NF‐κB pathway in human gastric cancer cells

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