Zerumbone Suppresses Human Colorectal Cancer Invasion and Metastasis via Modulation of FAk/PI3k/NFκB-uPA Pathway

Hosseini, Narges; Khoshnazar, A R Khoshbin; Saidijam, Massoud; Jalilian, Farid Azizi; Najafi, Rezvan; Mahdavinezhad, Ali; Ezati, Razie; Sotanian, Alireza; Amini, Razieh

doi:10.1080/01635581.2018.1540719

Cited by 14 publications

(10 citation statements)

References 32 publications

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“…Zerumbone induced IL-1β pathways through the expression of interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, which might be associated with the activation of c-Jun N-terminal kinase and extracellular signal-regulated protein kinase [85]. Further, zerumbone treatment on HCT-116 and SW48 cells showed its anti-metastatic potential through the inhibition of Fak/PI3k/NF-κB-uPA pathway [86].…”

Section: Molecular Targets Of Zerumbone Against Cancermentioning

confidence: 99%

Potential of Zerumbone as an Anti-Cancer Agent

et al. 2019

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Cancer is still a major risk factor to public health globally, causing approximately 9.8 million deaths worldwide in 2018. Despite advances in conventional treatment modalities for cancer treatment, there are still few effective therapies available due to the lack of selectivity, adverse side effects, non-specific toxicities, and tumour recurrence. Therefore, there is an immediate need for essential alternative therapeutics, which can prove to be beneficial and safe against cancer. Various phytochemicals from natural sources have been found to exhibit beneficial medicinal properties against various human diseases. Zerumbone is one such compound isolated from Zingiber zerumbet Smith that possesses diverse pharmacological properties including those of antioxidant, antibacterial, antipyretic, anti-inflammatory, immunomodulatory, as well as anti-neoplastic. Zerumbone has shown its anti-cancer effects by causing significant suppression of proliferation, survival, angiogenesis, invasion, and metastasis through the molecular modulation of different pathways such as NF-κB, Akt, and IL-6/JAK2/STAT3 (interleukin-6/janus kinase-2/signal transducer and activator of transcription 3) and their downstream target proteins. The current review briefly summarizes the modes of action and therapeutic potential of zerumbone against various cancers.

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Section: Molecular Targets Of Zerumbone Against Cancermentioning

confidence: 99%

Potential of Zerumbone as an Anti-Cancer Agent

et al. 2019

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“…38 Also, it has been revealed that Zerumbone suppresses human colorectal cancer invasion and metastasis via modulation of the FAK/PI3K/NF-κB-u-PA pathway. 39 Furthermore, a study has shown that Zerumbone mitigated the migration of pancreatic, breast, and renal cancer cells via inhibition of Jak2/Stat3, Notch2, and STAT3 signaling pathways. [40][41][42] Interestingly, our prior study found that Zerumbone inhibited tumor growth and exerted potential cytotoxicity against GBM cells through reactive oxygen species (ROS) generation.…”

Section: Discussionmentioning

confidence: 99%

Zerumbone, a ginger sesquiterpene, inhibits migration, invasion, and metastatic behavior of human malignant glioblastoma multiforme in vitro

et al. 2021

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The most widespread and challenging aggressive malignant tumor in the brain is glioblastoma multiforme (GBM). GBM is characterized, in particular, by significant intratumor cell variability, high growth rates, and widespread invasiveness within the surrounding normal brain parenchyma. The present study aimed to examine the impact of the natural product Zerumbone, a promising sesquiterpenoid phytochemical from Zingiber zerumbet, on U-87 MG GBM cells and its underlying molecular mechanisms. At sub-lethal doses, Zerumbone exerted a concentration-and time-dependent suppression of cell migration ability utilizing scratch wound closure assay; it also inhibited GBM cells' invasion using Transwell invasion assay in a concentration-dependent fashion. The enzymatic activity of matrix metalloproteinase (MMP)-2/-9 and their protein expression has also been reduced by administration of Zerumbone. Furthermore, Zerumbone was revealed to downregulate the mRNA expression level of IL-1β and MCP-1, two genes contributing to MMPs expression. We also found that Zerumbone exerted an inhibitory effect on the expression of Akt and total p44/42 MAPK (Erk1/Erk2) against U-87 MG cells.These findings collectively provide further proof for the possible molecular signaling basis of the antimetastatic effects of Zerumbone as a promising

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“…ZB suppressed the migration and invasion of colorectal cancer cells in vitro by inhibiting the focal adhesion kinase (FAK)/PI3K/NF-κB signaling pathway [78]. The FAKdependent signaling pathway helps tumor progression and consequent metastasis by causing cell migration, invasion, transition, and angiogenesis [79,80].…”

Section: Zerumbone (Zb)mentioning

confidence: 99%

Cancer Chemopreventive Role of Dietary Terpenoids by Modulating Keap1-Nrf2-ARE Signaling System—A Comprehensive Update

et al. 2021

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ROS, RNS, and carcinogenic metabolites generate excessive oxidative stress, which changes the basal cellular status and leads to epigenetic modification, genomic instability, and initiation of cancer. Epigenetic modification may inhibit tumor-suppressor genes and activate oncogenes, enabling cells to have cancer promoting properties. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that in humans is encoded by the NFE2L2 gene, and is activated in response to cellular stress. It can regulate redox homoeostasis by expressing several cytoprotective enzymes, including NADPH quinine oxidoreductase, heme oxygenase-1, UDP-glucuronosyltransferase, glutathione peroxidase, glutathione-S-transferase, etc. There is accumulating evidence supporting the idea that dietary nutraceuticals derived from commonly used fruits, vegetables, and spices have the ability to produce cancer chemopreventive activity by inducing Nrf2-mediated detoxifying enzymes. In this review, we discuss the importance of these nutraceuticals in cancer chemoprevention and summarize the role of dietary terpenoids in this respect. This approach was taken to accumulate the mechanistic function of these terpenoids to develop a comprehensive understanding of their direct and indirect roles in modulating the Keap1-Nrf2-ARE signaling system.

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Zerumbone Suppresses Human Colorectal Cancer Invasion and Metastasis via Modulation of FAk/PI3k/NFκB-uPA Pathway

Cited by 14 publications

References 32 publications

Potential of Zerumbone as an Anti-Cancer Agent

Potential of Zerumbone as an Anti-Cancer Agent

Zerumbone, a ginger sesquiterpene, inhibits migration, invasion, and metastatic behavior of human malignant glioblastoma multiforme in vitro

Cancer Chemopreventive Role of Dietary Terpenoids by Modulating Keap1-Nrf2-ARE Signaling System—A Comprehensive Update

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