Curcumin derivative WZ35 inhibits tumor cell growth via ROS-YAP-JNK signaling pathway in breast cancer

Wang, Lihua; Wang, Canwei; Tao, Zheying; Zhao, Liqian; Zhu, Zheng; Wu, Wencan; He, Ye; Chen, Hong; Zheng, Bin; Huang, Xiangjie; Yu, Yun; Yang, Linjun; Liang, Guang; Cui, Ri; Chen, Tongke

doi:10.1186/s13046-019-1424-4

Cited by 95 publications

(72 citation statements)

References 54 publications

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“…Current study presents that activation of the p38 and JNK can lead apoptotic effect in MCF-7 cells. The pathway is consistent with the route suggested by previous researches [21,53,[75][76][77][78][79][80][81]. Numerous natural products show anticancer activity by the cooperation and/or downstream the signals transduction of p38 and JNK, accompanying the apoptotic effect.…”

Section: Discussionsupporting

confidence: 90%

Activation of JNK and p38 in MCF-7 Cells and the In Vitro Anticancer Activity of Alnus hirsuta Extract

Ryu

Sung

et al. 2020

Molecules

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JNK and p38 are important mitogen-activated protein kinases (MAPKs) that respond to stress stimuli. The stress-activated MAPKs associated with apoptotic cell death play vital roles in mammalian cells. Alnus hirsuta, which contains abundant diarylheptanoids derivatives, is a valuable medicinal plant. The CHCl3 extract (AHC) containing platyphyllenone (1) and platyphyllone (3) as main compounds showed in vitro anticancer effects. We report the biological activities of A. hirsuta extract associated with the regulation of apoptosis and JNK and p38 in MCF-7 breast cancer cells. Levels of phospho-JNK and phospho-p38 by AHC treatment were evaluated by enzyme-linked immunosorbent assay (ELISA). ROS production, apoptotic effect, and DNA contents of the cells were measured by flow cytometry. The two diarylheptanoids 1 and 3 and the AHC extract exhibited cytotoxic effects on MCF-7 cells in MTT assay, with IC50 values of 18.1, 46.9, 260.0 μg/mL, respectively. AHC induced ROS generation and elevated the endogenous levels of phospho-JNK and phospho-p38. AHC resulted in apoptosis and cell cycle arrest. We suggest that the antitumor effect of A. hirsuta extract is achieved by apoptosis promotion and cell cycle arrest mediated by the activation of JNK and p38 signaling pathway via ROS generation.

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Section: Discussionsupporting

confidence: 90%

Activation of JNK and p38 in MCF-7 Cells and the In Vitro Anticancer Activity of Alnus hirsuta Extract

Ryu

Sung

et al. 2020

Molecules

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“…7). The present study revealed that the protein expression levels of YAP were decreased in the combination group, and previous studies have demonstrated that YAP is associated with the occurrence of breast cancer (69)(70)(71). YAP can enhance cell growth and tumor growth (72,73).…”

Section: Discussionsupporting

confidence: 80%

17‑AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA‑MB‑231 breast cancer cells

Zuo

Chen

et al. 2020

Oncol Rep

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Breast cancer is one of the most common malignancies that threaten the health of women. Although there are a few chemotherapies for the clinical treatment of breast cancer, these therapies are faced with the problems of drug-resistance and metastasis. Drug combination can help to reduce the adverse side effects of chemotherapies using single drugs, and also help to overcome common drug-resistance during clinical treatment of breast cancer. The present study reported the synergistic effect of the heat shock protein 90 inhibitor 17-AAG and the histone deacetylase 6 inhibitor Belinostat in triple-negative breast cancer (TNBC) MDA-MB-231 cells, by detection of proliferation, apoptosis and cell cycle arrest following treatment with this combination. Subsequently, RNA sequencing (RNA-seq) data was collected and analyzed to investigate the synergistic mechanism of this combination. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways revealed by RNA-seq data analysis, a wound-healing assay was used to investigate the effect of this combination on the migration of MDA-MB-231 cells. Compared with treatment with 17-AAG or Belinostat alone, both the viability inhibition and apoptosis rate of MDA-MB-231 cells were significantly enhanced in the combination group. The combination index values were <1 in three concentration groups. Revealed by the RNA-seq data analysis, the most significantly enriched KEGG pathways in the combination group were closely associated with cell migration. Based on these findings, the anti-migration effect of this combination was investigated. It was revealed that the migration of MDA-MB-231 cells was significantly suppressed in the combination group compared with in the groups treated with 17-AAG or Belinostat alone. In terms of specific genes, the mRNA expression levels of TEA domain family proteins were significantly decreased in the combination group, whereas the phosphorylation of YY1 associated protein 1 and modulator of VRAC current 1 was significantly enhanced in the combination group. These alterations may help to explain the anti-migration effect of this combination. Belinostat has already been approved as a treatment for T-cell lymphoma and 17-AAG is undergoing clinical trials. These findings could provide a beneficial reference for the clinical treatment of patients with TNBC.

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“…Recurrence and chemoresistance have restricted the efficacy of currently applied treatment in breast cancer therapy [ 97 , 98 , 99 , 100 ]. Natural products have demonstrated an excellent inhibitory effect on both proliferation and metastasis of breast cancer [ 101 , 102 , 103 , 104 ]. A combination of chrysin and silibinin is beneficial in suppressing breast cancer malignancy via decreasing cancer proliferation.…”

Section: Chrysin and Cancermentioning

confidence: 99%

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

et al. 2020

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Pharmacological profile of phytochemicals has attracted much attention to their use in disease therapy. Since cancer is a major problem for public health with high mortality and morbidity worldwide, experiments have focused on revealing the anti-tumor activity of natural products. Flavonoids comprise a large family of natural products with different categories. Chrysin is a hydroxylated flavonoid belonging to the flavone category. Chrysin has demonstrated great potential in treating different disorders, due to possessing biological and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, etc. Over recent years, the anti-tumor activity of chrysin has been investigated, and in the present review, we provide a mechanistic discussion of the inhibitory effect of chrysin on proliferation and invasion of different cancer cells. Molecular pathways, such as Notch1, microRNAs, signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappaB (NF-κB), PI3K/Akt, MAPK, etc., as targets of chrysin are discussed. The efficiency of chrysin in promoting anti-tumor activity of chemotherapeutic agents and suppressing drug resistance is described. Moreover, poor bioavailability, as one of the drawbacks of chrysin, is improved using various nanocarriers, such as micelles, polymeric nanoparticles, etc. This updated review will provide a direction for further studies in evaluating the anti-tumor activity of chrysin.

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Curcumin derivative WZ35 inhibits tumor cell growth via ROS-YAP-JNK signaling pathway in breast cancer

Cited by 95 publications

References 54 publications

Activation of JNK and p38 in MCF-7 Cells and the In Vitro Anticancer Activity of Alnus hirsuta Extract

Activation of JNK and p38 in MCF-7 Cells and the In Vitro Anticancer Activity of Alnus hirsuta Extract

17‑AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA‑MB‑231 breast cancer cells

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

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