Cinnamaldehyde induces apoptosis and reverses epithelial-mesenchymal transition through inhibition of Wnt/β-catenin pathway in non-small cell lung cancer

Wu, Cunen; Zhuang, Yingping; Jiang, Shengbing; Tian, Fang; Teng, Yuhao; Chen, Zhanghua; Zheng, Pei-Qiu; Liu, Shenlin; Zhou, Jin‐Yong; Wu, Jian; Wang, Ruiping; Zou, Xi

doi:10.1016/j.biocel.2017.01.005

Cited by 46 publications

(27 citation statements)

References 36 publications

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“…Greater than 80% of the essential oil of cinnamon is constituted by CA, and the various pharmacological properties of cinnamon are attributed to CA including its antitumorigenic activity. In addition to its proapoptotic and antiproliferative activity, a few studies have also focused on the antimetastatic activity of cinnamon . Cinnamon extract has been shown to possess antiangiogenic activity in a few in vitro and in vivo studies .…”

Section: Introductionmentioning

confidence: 99%

The inhibition of hypoxia‐induced angiogenesis and metastasis by cinnamaldehyde is mediated by decreasing HIF‐1α protein synthesis via PI3K/Akt pathway

et al. 2019

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Tumor hypoxia is positively correlated with tumor aggressiveness and hence is a negative prognostic factor in cancer. As normal cells usually do not experience such low oxygen levels, hypoxic cell signaling has attracted significant attention for the development of tumor-selective treatment strategies. In response to hypoxia, the master transcriptional regulator, HIF-1α plays central role in cellular adaptation by transactivating several crucial downstream target genes, which are involved in angiogenesis, metastasis, and EMT. In this study, we investigated the effect of cinnamaldehyde (CA), the main active ingredient of Cinnamon cassia bark extract, on hypoxia-induced angiogenesis and metastasis. The study in vitro comprised two cell lines, viz, sarcoma 180 and B16F10 melanoma, which were further confirmed in their respective transplantable in vivo models. Results show that CA administration inhibited tumor angiogenesis, EMT, and metastasis. At the molecular level, this was accompanied by a reduction in VEGF secretion, VEGF receptor (FLK) phosphorylation, matrix metalloproteinase (MMP) expression, and activity as well as a reduction in the EMT-related factors TWIST and ZEB1. Next, we focused our study particularly on the modulation of HIF-1 α by CA, which revealed that CA decreased HIF-1 α protein level by inhibiting its synthesis without affecting its proteasomal degradation. Furthermore, the PI3/Akt/m-TOR pathway, which plays an important role in HIF-1α transcription and translation, was also inhibited by CA both in vitro and in vivo. Thus, it can be concluded that CA decreased angiogenesis and metastasis in tumor cells by inhibiting HIF-1α protein accumulation probably by targeting the PI3/Akt/mTOR pathway. © 2019 BioFactors, 45(3):401-415, 2019

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Section: Introductionmentioning

confidence: 99%

The inhibition of hypoxia‐induced angiogenesis and metastasis by cinnamaldehyde is mediated by decreasing HIF‐1α protein synthesis via PI3K/Akt pathway

et al. 2019

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“…Essential oils extracted from C. cassia Presl had antinociceptive and anti‐inflammatory properties and decreased the levels of cytokines, TNF‐α, IL‐1β, and prostaglandin E2 in carrageenan‐induced mouse paw skin tissue (Sun et al, ). Cinnamaldehyde inhibited proliferation of colorectal cancer cells SW480, HCT116, and LoVo; human breast cancer cells MCF‐7; and human non‐small lung cancer cells (Li, Teng, et al, ; Rad et al, ; Wu et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Cinnamaldehyde inhibited proliferation of colorectal cancer cells SW480, HCT116, and LoVo; human breast cancer cells MCF-7; and human non-small lung cancer cells (Li, Teng, et al, 2016;Rad et al, 2015;Wu et al, 2017). Zhou, & Liu, 2017).…”

Section: Figurementioning

confidence: 98%

Herbal medicine for hand–foot syndrome induced by fluoropyrimidines: A systematic review and meta‐analysis

Deng

Sun

2018

Phytotherapy Research

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The aims of this study were to evaluate the efficacy of herbal medicine for the prevention and management of hand-foot syndrome (HFS) induced by fluoropyrimidines and to identify herbs associated with HFS alleviation for further research. The PubMed, Cochrane, Springer, China National Knowledge Infrastructure, and Wanfang databases were searched up to May 2017 for randomized controlled trials (RCTs) that evaluated herbal medicine for relieving HFS in patients undergoing fluoropyrimidine-based chemotherapy. Study evaluation and synthesis methods were in accordance with the Cochrane Handbook, and data were analyzed using RevMan 5.3. In total, 35 RCTs (2,668 participants) were included. Meta-analysis showed that the addition of herbal medicine significantly reduced the incidences of all-grade and high-grade HFS. The total effective rate and complete remission rate of HFS patients increased significantly with herbal medicine arm. Further sensitivity analysis identified Paeoniae Radix Alba, Carthami Flos, Cinnamomi Ramulus, and Glycyrrhizae Radix et Rhizoma as being consistently associated with significant reductions in HFS incidence without important heterogeneity. However, the lack of blinding in most studies may have led to overestimation of these effects. More high-quality RCTs and experimental research are needed to confirm and investigate the efficacy of the herbs identified in this study.

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“…CA has shown anticancer effects on lung cancer, rectal cancer, and oral cancer in vitro and in vivo [18][19][20][21]. It has a similar structure to curcumin, which influences the inhibition of visfatin protein expression [22].…”

Section: Introductionmentioning

confidence: 99%

Dietary Antioxidant Trans-Cinnamaldehyde Reduced Visfatin-Induced Breast Cancer Progression: In Vivo and In Vitro Study

et al. 2019

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Excessive growth of cancer cells is the main cause of cancer mortality. Therefore, discovering how to inhibit cancer growth is an important research topic. Recently, the newly discovered adipokine, known as nicotinamide phosphoribosyl transferase (NAMPT, visfatin), which has been associated with metabolic syndrome and obesity, has also been found to be a major cause of cancer proliferation. Therefore, inhibition of NAMPT and reduction of Nicotinamide adenine dinucleotide (NAD) synthesis is one strategy for cancer therapy. Cinnamaldehyde (CA), as an antioxidant and anticancer natural compound, may have the ability to inhibit visfatin. The breast cancer cell line and xenograft animal models were treated under different dosages of visfatin combined with CA and FK866 (a visfatin inhibitor) to test for cell toxicity, as well as inhibition of tumor-related proliferation of protein expression. In the breast cancer cell and the xenograft animal model, visfatin significantly increased proliferation-related protein expression, but combination with CA or FK866 significantly reduced visfatin-induced carcinogenic effects. For the first time, a natural compound inhibiting extracellular and intracellular NAMPT has been demonstrated. We hope that, in the future, this can be used as a potential anticancer compound and provide further directions for research.

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Cinnamaldehyde induces apoptosis and reverses epithelial-mesenchymal transition through inhibition of Wnt/β-catenin pathway in non-small cell lung cancer

Cited by 46 publications

References 36 publications

The inhibition of hypoxia‐induced angiogenesis and metastasis by cinnamaldehyde is mediated by decreasing HIF‐1α protein synthesis via PI3K/Akt pathway

The inhibition of hypoxia‐induced angiogenesis and metastasis by cinnamaldehyde is mediated by decreasing HIF‐1α protein synthesis via PI3K/Akt pathway

Herbal medicine for hand–foot syndrome induced by fluoropyrimidines: A systematic review and meta‐analysis

Dietary Antioxidant Trans-Cinnamaldehyde Reduced Visfatin-Induced Breast Cancer Progression: In Vivo and In Vitro Study

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