Cinnamaldehyde enhances apoptotic effect of oxaliplatin and reverses epithelial-mesenchymal transition and stemnness in hypoxic colorectal cancer cells

Wu, Cunen; Zhuang, Yingping; Zhou, Jin‐Yong; Liu, Shenlin; Wang, Ruiping; Shu, Ping

doi:10.1016/j.yexcr.2019.111500

Cited by 24 publications

(13 citation statements)

References 27 publications

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“…Previous studies have shown that cinnamaldehyde and cinnamaldehyde-derived compounds are drug candidates for the development of anticancer drugs, which has attracted extensive research attention (Hong et al, 2016). Cinnamaldehyde can improve the anti-cancer efficacy of oxaliplatin by promoting the apoptosis of colorectal cancer cells in vivo and in vitro (Wu et al, 2019). As an antioxidant, cinnamaldehyde can inhibit the spread of cancer by inhibiting the expression of extracellular and intracellular fat factor nicotinamide phosphoribosyltransferase (Chiang et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Targets and Mechanism Used by Cinnamaldehyde, the Main Active Ingredient in Cinnamon, in the Treatment of Breast Cancer

Liu

Wan

et al. 2020

Front. Pharmacol.

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Background: Breast cancer has become one of the most common malignant tumors in women owing to its increasing incidence each year. Clinical studies have shown that Cinnamomum cassia (L.) J. Presl (cinnamon) has a positive influence on the prevention and treatment of breast cancer.Aim: We aimed to screen the potential targets of cinnamon in the treatment of breast cancer through network pharmacology and explore its potential therapeutic mechanism through cell experiments.Methods: We used the TCMSP, TCM Database @ Taiwan, and TCMID websites and established the active ingredient and target database of cinnamon. Thereafter, we used the GeneCards and OMIM databases to establish a breast cancer-related target database, which matched the cinnamon target database. Based on the matching results, the STRING database was used to analyze the interaction between the targets, and the biological information annotation database was used to analyze the biological process of the target (gene ontology) and the pathway enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG). After establishing the layout of the analysis, we used Cytoscape 3.6.0 software for network analysis. Finally, the cell experiment was used to verify the anti-breast cancer effect of cinnamaldehyde.Results: Our research showed that the main components of cinnamon, including cinnamaldehyde, can play a role in the treatment of breast cancer through 59 possible important targets. Subsequently, enrichment analysis by gene ontology and Kyoto Encyclopedia of Genes and Genomes showed that 83 cell biological processes and 37 pathways were associated with breast cancer (p < 0.05), including the peroxisome proliferator-activated receptor and PI3K-Akt pathway, which are closely related to tumor cell apoptosis. In vitro cell verification experiments showed that cinnamaldehyde can significantly inhibit cell proliferation, change cell morphology, inhibit cell migration and invasion ability, and promote cell apoptosis.Conclusion: Our results showed that cinnamaldehyde is a potential novel drug for the treatment and prevention of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Targets and Mechanism Used by Cinnamaldehyde, the Main Active Ingredient in Cinnamon, in the Treatment of Breast Cancer

Liu

Wan

et al. 2020

Front. Pharmacol.

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“…The Wnt pathway can promote EMT in CRC cells by activating MDR1, which in turn increases CRC resistance to oxaliplatin, but is there a targeted therapeutic agent for the Wnt pathway? Wu et al 45 reported the synergistic effects of cinnamaldehyde and L-OHP inhibited hypoxia-activated Wnt/β-catenin signaling, reversed EMT, activated CsC, and reduced the development of L-OHP resistance. CRC patients with KRAS mutations are insensitive to cetuximab and panitumumab, 46 and the potent and selective Wnt/β-catenin inhibitor KYA1797K activates GSK3β and degrades small β-catenin and RAS molecules to increase the sensitivity of tumors with KRAS mutations to cetuximab and panitumumab.…”

Section: Treatment and Drug Resistance Of Crc Associated With Emtmentioning

confidence: 99%

Research Progress of Epithelial-mesenchymal Transition Treatment and Drug Resistance in Colorectal Cancer

2022

Technol Cancer Res Treat

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Colorectal cancer (CRC) is one of the most common malignancies in the world that seriously affects human health. Activation of epithelial-mesenchymal transition (EMT) is a physiological phenomenon during embryonic development that is essential for cell metastasis. EMT participates in various biological processes associated with trauma repair, organ fibrosis, migration, metastasis, and infiltration of tumor cells. EMT is a new therapeutic target for CRC; however, some patients with CRC develop resistance to some drugs due to EMT. This review focuses specifically on the status of treatments that target the EMT process and its role in the therapeutic resistance observed in patients with CRC.

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“…Furthermore, a serine protease TKP has a repressive effect on CRC cell invasion and metastasis by targeting MMP2 and MMP9, and is mediated by blockade of both Wnt/β-catenin and Hedgehog/Gli1 signaling ( Sun et al, 2020 ). In addition, cinnamaldehyde has been certified to have potential adjuvant effect on CRC cells in combination with oxaliplatin through blocking the Wnt/β-catenin pathway and enhancing the susceptibility of oxaliplatin in the hypoxic environment ( Wu et al, 2019 ).…”

Section: Regulatory Mechanism Of Active Compounds Against Metastatic Crcmentioning

confidence: 99%

Potential Role of Traditional Chinese Medicines by Wnt/β-Catenin Pathway Compared With Targeted Small Molecules in Colorectal Cancer Therapy

et al. 2021

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Colorectal cancer (CRC) has become a global public health problem because of its high incidence and mortality rate worldwide. The previous clinical treatment for CRC mainly involves conventional surgery, chemotherapy, and radiotherapy. With the development of tumor molecular targeted therapy, small molecule inhibitors present a great advantage in improving the survival of patients with advanced CRC. However, various side effects and drug resistance induced by chemotherapy are still the major obstacles to improve the clinical benefit. Thus, it is crucial to find new and alternative drugs for CRC treatment. Traditional Chinese medicines (TCMs) have been proved to have low toxicity and multi-target characteristics. In the last few decades, an increasing number of studies have demonstrated that TCMs exhibit strong anticancer effects in both experimental and clinical models and may serve as alternative chemotherapy agents for CRC treatment. Notably, Wnt/β-catenin signaling pathway plays a vital role in the initiation and progression of CRC by modulating the stability of β-catenin in the cytoplasm. Targeting Wnt/β-catenin pathway is a novel direction for developing therapies for CRC. In this review, we outlined the anti-tumor effects of small molecular inhibitors on CRC through Wnt/β-catenin pathway. More importantly, we focused on the potential role of TCMs against tumors by targeting Wnt/β-catenin signaling at different stages of CRC, including precancerous lesions, early stage of CRC and advanced CRC. Furthermore, we also discussed perspectives to develop potential new drugs from TCMs via Wnt/β-catenin pathway for the treatment of CRC.

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Cinnamaldehyde enhances apoptotic effect of oxaliplatin and reverses epithelial-mesenchymal transition and stemnness in hypoxic colorectal cancer cells

Cited by 24 publications

References 27 publications

Targets and Mechanism Used by Cinnamaldehyde, the Main Active Ingredient in Cinnamon, in the Treatment of Breast Cancer

Targets and Mechanism Used by Cinnamaldehyde, the Main Active Ingredient in Cinnamon, in the Treatment of Breast Cancer

Research Progress of Epithelial-mesenchymal Transition Treatment and Drug Resistance in Colorectal Cancer

Potential Role of Traditional Chinese Medicines by Wnt/β-Catenin Pathway Compared With Targeted Small Molecules in Colorectal Cancer Therapy

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