Japonicone A inhibits the growth of non-small cell lung cancer cells via mitochondria-mediated pathways

Du, Yan; Gong, Jiannan; Tian, Xinggui; Yan, Xiaomei; Guo, Tao; Huang, Min; Zhang, Bingtai; Hu, Xiaoyun; Liu, Hui; Wang, Yinping; Li, Jianqiang; Li, Maolan

doi:10.1007/s13277-015-3439-6

Cited by 21 publications

(14 citation statements)

References 25 publications

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“…The initiation of the intrinsic pathway is associated with pro-apoptotic factors, including B-cell lymphoma 2 (Bcl-2)-associated X protein and Bcl-2-associated death promoter, which leads to an increased permeability of the mitochondria membrane, loss of membrane potential and the release of cytochrome c into the cytosol (20). The intrinsic pathway is associated with activated caspase-3, whereas the extrinsic pathway is associated with the activation of caspase-8 (21). In the results of the present study, it was indicated that the relative activities of caspase-8 remained unchanged (data not shown), therefore it may be that the intrinsic pathway was involved in the process, which is a focus of future study.…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA NNT‑AS1 contributes to cell proliferation, metastasis and apoptosis in human ovarian cancer

Huang

Shi

2018

Oncol Lett

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Ovarian cancer is a markedly heterogeneous malignancy characterized by various histological subtypes. Molecular biomarkers have been indicated to serve significant functions in the early diagnosis and treatment of early-stage ovarian cancer. However, the detailed mechanism underlying the tumorigenesis of ovarian cancer remains unclear. The present study aimed to identify a novel long non-coding RNA in patients with ovarian cancer. Nicotinamide nucleotide transhydrogenase-antisense 1 (NNT-AS1) was markedly downregulated in patients with ovarian cancer and in cultured human ovarian cancer cells. Knockdown of NNT-AS1 in the human ovarian cancer cell lines HO-8910 and SK-OV-3 promoted colony formation and arrested the cell cycle at G/G phase. Furthermore, Transwell demonstrated that the downregulation of NNT-AS1 increased cell migration and invasion by ~60 and 70%, respectively, in HO-8910 and SK-OV-3 cells. Furthermore, cell apoptosis was inhibited by the transfection of siNNT-AS1 in the two cell lines, whereas the relative activities of caspase-3 and caspase-9 were decreased. These results indicated a protective function of NNT-AS1 in human ovarian cancer, providing novel insights into the diagnosis and treatment of ovarian cancer in clinical settings.

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Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA NNT‑AS1 contributes to cell proliferation, metastasis and apoptosis in human ovarian cancer

Huang

Shi

2018

Oncol Lett

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“…It has also been observed that JapA is safe and effective in treating other human cancers containing high expression levels of MDM2, e.g. , Burkitt lymphoma and lung cancer [ 20 – 21 ]. Mechanistically, JapA decreases MDM2 protein stability and inhibits MDM2 transcription, regardless of p53 status of the cells or tumors [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibiting NFAT1 for breast cancer therapy: New insights into the mechanism of action of MDM2 inhibitor JapA

et al. 2015

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Transcription factor NFAT1 has been recently identified as a new regulator of the MDM2 oncogene. Targeting the NFAT1-MDM2 pathway represents a novel approach to cancer therapy. We have recently identified a natural product MDM2 inhibitor, termed JapA. As a specific and potent MDM2 inhibitor, JapA inhibits MDM2 at transcriptional and post-translational levels. However, the molecular mechanism remains to be fully elucidated for its inhibitory effects on MDM2 transcription. Herein, we reported that JapA inhibited NFAT1 and NFAT1-mediated MDM2 transcription, which contributed to the anticancer activity of JapA. Its effects on the expression and activity of NFAT1 were examined in various breast cancer cell lines in vitro and in MCF-7 and MDA-MB-231 xenograft tumors in vivo. The specificity of JapA in targeting NFAT1 and NFAT1-MDM2 pathway and the importance of NFAT1 inhibition in JapA's anticancer activity were demonstrated using NFAT1 overexpression and knockdown cell lines and the pharmacological activators and inhibitors of NFAT1 signaling. Our results indicated that JapA inhibited NFAT1 signaling in breast cancer cells in vitro and in vivo, which plays a pivotal role in its anticancer activity. JapA inhibited the nuclear localization of NFAT1, disrupted the NFAT1-MDM2 P2 promoter complex, and induced NFAT1 proteasomal degradation, resulting in the repression of MDM2 transcription. In conclusion, JapA is a novel NFAT1 inhibitor and the NFAT1 inhibition is responsible for the JapA-induced repression of MDM2 transcription, contributing to its anticancer activity. The results may pave an avenue for validating the NFAT1-MDM2 pathway as a novel molecular target for cancer therapy.

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“…In addition antiinflammatory properties of Tanacetum vulgare [27], Inula helenium L [28], Melissa officinalis [17], Artemisia vulgaris L [29] can all increase oxidative stress and induce mitochondrial-related apoptosis. These compounds have been traditionally used in anti-cancer therapy.…”

Section: Resultsmentioning

confidence: 99%

Effects of herbal multicomponent dietary supplement in experimental pneumonia

Serebrovska¹,

Swanson²,

Portnichenko³

et al. 2018

Fiziol Zh

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Japonicone A inhibits the growth of non-small cell lung cancer cells via mitochondria-mediated pathways

Cited by 21 publications

References 25 publications

Long non‑coding RNA NNT‑AS1 contributes to cell proliferation, metastasis and apoptosis in human ovarian cancer

Long non‑coding RNA NNT‑AS1 contributes to cell proliferation, metastasis and apoptosis in human ovarian cancer

Inhibiting NFAT1 for breast cancer therapy: New insights into the mechanism of action of MDM2 inhibitor JapA

Effects of herbal multicomponent dietary supplement in experimental pneumonia

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