Molecular mechanisms of Polyphyllin I-induced apoptosis and reversal of the epithelial–mesenchymal transition in human osteosarcoma cells

Chang, Junli; Wang, Hongshen; Wang, Xianyang; Zhao, Yongjian; Zhao, Dongfeng; Wang, Chenglong; Li, Yimian; Zhang, Yang; Lü, Sheng; Zeng, Qinghua; Zimmerman, Jacquelyn W.; Shi, Qi; Wang, Yongjun; Yang, Yanping

doi:10.1016/j.jep.2015.05.006

Cited by 54 publications

(57 citation statements)

References 40 publications

(45 reference statements)

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“…It was also reported that Polyphyllin was able to reverse EMT in osteosarcoma cells. 21) ZH-2, a compound derived from Polyphyllin VII posses anti-chemoresistance properties by inhibiting the EMT. 25) Furthermore, we found the inhibitory effect of PPI on tumor growth in an in vivo xenograft model of EMT-driven acquired resistance to erlotinib.…”

Section: Discussionmentioning

confidence: 99%

“…Polyphyllin I (PPI) displayed inhibitory effect on various types of cancer, including hepatocarcinoma, 19) non-small cell lung cancer, 20) osteosarcoma, 21) chronic myeloid leukemia, 22) ovarian cancer, 23) glioma cells 24) and so forth. Through the multiple pathways, including an increase of cell cycle arrest and apoptosis, PPI ultimately led to tumor inhibition.…”

mentioning

confidence: 99%

“…Recently, Chang et al reported that Polyphyllin was able to reverse EMT in osteosarcoma cells. 21) ZH-2, a compound derived from Polyphyllin VII posses anti-chemoresistance properties by inhibiting the EMT. 25) Inspired by this study, we analyzed the effects of PPI on HCC827 erlotinib-resistant (ER) cells to determine whether PPI can prevent EMT and conquer acquired resistance to EGFR-TKI treatment.…”

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confidence: 99%

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Polyphyllin I Overcomes EMT-Associated Resistance to Erlotinib in Lung Cancer Cells <i>via</i> IL-6/STAT3 Pathway Inhibition

Lou

Yan

Zhu

et al. 2017

Biological & Pharmaceutical Bulletin

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Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is the most important limiting factor for treatment efficiency in EGFR-mutant non-small cell lung cancer (NSCLC). Much work has linked the epithelial-mesenchymal transition (EMT) to the emergence of drug resistance, consequently, ongoing research has been focused on exploring the therapeutic options to reverse EMT for delaying or preventing drug resistance. Polyphyllin I (PPI) is a natural compound isolated from Paris polyphylla rhizomes and displayed anti-cancer properties. In the current work, we aimed to testify whether PPI could reverse EMT and overcome acquired EGFR-TKI resistance. We exposed HCC827 lung adenocarcinoma cells to erlotinib which resulted in acquired resistance with strong features of EMT. PPI effectively restored drug sensitivity of cells that obtained acquired resistance. PPI reversed EMT and decreased interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway activation in erlotinib-resistant cells. Moreover, addition of IL-6 partially abolished the sensitization response of PPI. Furthermore, co-treatment of erlotinib and PPI completed abrogation of tumor growth in xenografts, which was associated with EMT reversal. In conclusion, PPI serves as a novel solution to conquer the EGFR-TKI resistance of NSCLC via reversing EMT by modulating IL-6/STAT3 signaling pathway. Combined PPI and erlotinib treatment provides a promising future for lung cancer patients to strengthen drug response and prolong survival.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Polyphyllin I Overcomes EMT-Associated Resistance to Erlotinib in Lung Cancer Cells <i>via</i> IL-6/STAT3 Pathway Inhibition

Lou

Yan

Zhu

et al. 2017

Biological & Pharmaceutical Bulletin

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“…Inhibition of the EMT and NF-kB/Snail signaling pathway has been shown to significantly suppress metastasis in multiple cancer cell types, such as gastric adenocarcinoma cells SGC-7901 (Zhu et al, 2015) and breast cancer cells A2780 (Liu et al, 2015a). Moreover, suppression of the NF-kB activity and EMT-related proteins, such as vimentin, Snail, and Slug, has been shown to suppress metastasis in osteosarcoma cell lines MG-63, Saos-2, and U-2OS (Chang et al, 2015), indicating that cancer metastasis can be effectively suppressed by inhibiting the EMT and NF-kB/Snail signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition

Feng¹,

Guo²

2016

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to investigate the expression of T-cell immunoglobulin mucin domain molecule-3 (Tim-3) in osteosarcoma tissues, and analyze its effect on cell proliferation and metastasis in an osteosarcoma cell line. Tim-3 mRNA and protein expression in osteosarcoma tissue was detected by reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. Additionally, the cell viability, apoptosis rate, and invasive ability of the osteosarcoma cell line MG-63 were tested using the methyl thiazolyl tetrazolium assay, Annexin V-propidium iodide flow cytometry, and a Transwell assay, respectively, following Tim-3 interference using small interfering RNA (siRNA). We also analyzed the expression of Snail, E-cadherin, vimentin, and nuclear factor (NF)-kB in the cells by western blot. We observed that Tim-3 mRNA and protein was significantly overexpressed in osteosarcoma tissues, compared to the adjacent normal tissue (P < 0.01). Moreover, MG-63 cells transfected with the Tim-3 siRNA presented lower cell viability, a greater number of apoptotic cells, and decreased invasive ability (P < 0.01), compared to control cells. Additionally, we observed a decrease in Snail and vimentin expression, an increase in the E-cadherin level, and an increase in NF-kB p65 phosphorylation (P < 0.01) in Tim-3 siRNA-transfected MG-63 cells. Based on these results, we concluded that Tim-3 is highly expressed in osteosarcoma tissue. Moreover, we speculated that interfering in Tim-3 expression could significantly suppress osteosarcoma cell (MG-63) proliferation and metastasis via the NF-kB/Snail signaling pathway and epithelial-mesenchymal transition.

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“…Exposure of OS cells to PPI triggered inactivation of the intrinsic nuclear component κB (NF-κB) and activation of unfolded protein response/endoplasmic reticulum stress signaling cascade in OS cells, followed by downregulation of anti-apoptotic proteins, with up regulation of pro-apoptotic proteins. Thus, it can be used for OS treatment [36].…”

Section: 7dihydroxy3'4'6trimethoxymentioning

confidence: 99%

Herbal Remedy for Osteosarcoma - Challenging Evolution

Pichaiyan

Mariyappan

Saravanan

et al. 2018

Asian J Pharm Clin Res

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Bone cancer is the extremely rare type, which accounts for about 0.2% of all cancer. They metastasize the cancer cells to the bone parts which have an especially crucial mechanism of action while treating. It is treated with the advanced drugs, have effluent side effects when compared to the medicinal plants and phytoconstituents. The review effectively deals that the mechanism of action of different medicinal plants include Phyllanthus urinaria, Aralia elata, Punica granatum, Anemone altaica, and Potentilla chinensis and the phytoconstituents include corosolic acid, shikonin, thymoquinone, aloperine, and withaferin A. This review provides the detailed information about the importance of medicinal herbs in the treatment of bone cancer, besides the mechanism of action of several phytoconstituents in different cell lines used. In future, it is more useful for evaluating the treatment of bone cancer with phytoconstituents.

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Molecular mechanisms of Polyphyllin I-induced apoptosis and reversal of the epithelial–mesenchymal transition in human osteosarcoma cells

Cited by 54 publications

References 40 publications

Polyphyllin I Overcomes EMT-Associated Resistance to Erlotinib in Lung Cancer Cells <i>via</i> IL-6/STAT3 Pathway Inhibition

Polyphyllin I Overcomes EMT-Associated Resistance to Erlotinib in Lung Cancer Cells <i>via</i> IL-6/STAT3 Pathway Inhibition

Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition

Herbal Remedy for Osteosarcoma - Challenging Evolution

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