Ovatodiolide suppresses nasopharyngeal cancer by targeting stem cell-like population, inducing apoptosis, inhibiting EMT and dysregulating JAK/STAT signaling pathway

Liu, Shao‐Cheng; Huang, Chih Ming; Bamodu, Oluwaseun Adebayo; Lin, Chun–Shu; Liu, Bing Lan; Tzeng, Yew Min; Tsai, Jo Ting; Lee, Wei Hwa; Chen, Tsung Ming

doi:10.1016/j.phymed.2018.05.007

Cited by 37 publications

(25 citation statements)

References 22 publications

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“…It is reported that IL-6 can activate lncRNA DANCR through the STAT3 pathway, forming a positive feedback loop, enhancing the invasion and proliferation ability of NPC cells in vitro. 153 Liu et al 154 indicated that ovatodiolide could significantly inhibit the JAK2/STAT3 signal pathway, upregulate the level of Bax and Slug and decrease the level of Bcl-xL, c-Myc, and cyclin D1, which significantly reduces the cancer stem cell characteristics of NPC cells together with survival, proliferation, invasion, migration, and EMT inhibited, and promote the apoptosis of NPC cells.…”

Section: Stat3 Pathwaymentioning

confidence: 99%

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

Kang

Ren

et al. 2020

Sig Transduct Target Ther

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Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma of the head and neck region which mainly distributes in southern China and Southeast Asia and has a crucial association with the Epstein–Barr virus. Based on epidemiological data, both incidence and mortality of NPC have significantly declined in recent decades grounded on the improvement of living standard and medical level in an endemic region, in particular, with the clinical use of individualized chemotherapy and intensity-modulated radiotherapy (IMRT) which profoundly contributes to the cure rate of NPC patients. To tackle the challenges including local recurrence and distant metastasis in the current NPC treatment, we discussed the implication of using targeted therapy against critical molecules in various signal pathways, and how they synergize with chemoradiotherapy in the NPC treatment. Combination treatment including targeted therapy and IMRT or concurrent chemoradiotherapy is presumably to be future options, which may reduce radiation or chemotherapy toxicities and open new avenues for the improvement of the expected functional outcome for patients with advanced NPC.

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Section: Stat3 Pathwaymentioning

confidence: 99%

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

Kang

Ren

et al. 2020

Sig Transduct Target Ther

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“…The modest inhibitory activity towards solid cancer cells in vitro is prevalent in compounds with α‐methylene‐γ‐lactone units, as exemplified by the active component of ACT001, MCL (Figure A) which showed IC 50 values of approximately 20 μ m against various glioblastoma cells . The reason for this may its molecular mechanism to form a covalent bond with multitarget proteins in diverse oncogenic signaling pathways, such as Wnt/β‐catenin, ROS, NF‐κB,and JAK/STAT as validated by recent research, rather than a single‐target cytotoxic agent. The most attractive feature of ovatodiolide is its selective inhibitory activity towards CSCs.…”

Section: Figurementioning

confidence: 91%

Ovatodiolides: Scalable Protection‐Free Syntheses, Configuration Determination, and Biological Evaluation against Hepatic Cancer Stem Cells

Xiang

Ding

et al. 2019

Angewandte Chemie

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Ac oncise,s calable,s ix-step (longest linear sequence) synthetic route to ovatodiolide scaffolds was developed for the first time.T his protecting-group-free route features tandem ring-opening metathesis/ring-closing metathesis reactions to install the macrocycle-fused butenolide ring and at andem allylboration/lactonization to build the amethylene-g-lactone.Our syntheses have enabled the determination of the hitherto unknown stereochemical configurations of this family of natural products.P reliminary tests of structure-activity relationships were conducted with four natural ovatodiolides and three analogues.F urther assays indicated that the synthetic natural product isoovatodiolide can significantly decrease the population of hepatic cancer stem cells and reduce the tumorsphere-forming capability of HepG2 cells.

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“…A study found that the inhibition of colony formation and motility in NPC cells was correlated with decreased expression of p-FAK and increased expression of E-cadherin. 73 In another research, downregulation of E-cadherin along with enhanced cytoskeletal rearrangement and cell polarity was associated with the activation of FAK, thereby promoting cell migration. 74 RACK1 protein has been found to play an essential role in increasing the proliferation and invasion of NPC by regulating the PI3K/Akt/FAK signaling pathway.…”

Section: Mechanisms Of Fak In Hnscc Development and Metastasismentioning

confidence: 94%

<p>Role of Focal Adhesion Kinase in Head and Neck Squamous Cell Carcinoma and Its Therapeutic Prospect</p>

Zhang¹,

Sun²

2020

OTT

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Head and neck cancers are one of the most prevalent cancers globally. Among them, head and neck squamous cell carcinoma (HNSCC) accounts for approximately 90% of head and neck cancers, which occurs in the oral cavity, oral pharynx, hypopharynx and larynx. The 5-year survival rate of HNSCC patients is only 63%, mainly because about 80-90% of patients with advanced HNSCC tend to suffer from local recurrence or even distant metastasis. Despite the more in-depth understanding of the molecular mechanisms underlying the occurrence and progression of HNSCC in recent years, effective targeted therapies are unavailable for HNSCC, which emphasize the urgent demand for studies in this area. Focal adhesion kinase (FAK) is an intracellular non-receptor tyrosine kinase that contributes to oncogenesis and tumor progression by its significant function in cell survival, proliferation, adhesion, invasion and migration. In addition, FAK exerts an effect on the tumor microenvironment, epithelial-mesenchymal transition, radiation (chemotherapy) resistance, tumor stem cells and regulation of inflammatory factors. Moreover, the overexpression and activation of FAK are detected in multiple types of tumors, including HNSCC. FAK inhibition can induce cell cycle arrest and apoptosis, significantly decrease cell growth, invasion and migration in HNSCC cell lines. In this article, we mainly review the research progress of FAK in the occurrence, development and metastasis of HNSCC, and put forward the prospects for the therapeutic targets of HNSCC.

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Ovatodiolide suppresses nasopharyngeal cancer by targeting stem cell-like population, inducing apoptosis, inhibiting EMT and dysregulating JAK/STAT signaling pathway

Cited by 37 publications

References 22 publications

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

Ovatodiolides: Scalable Protection‐Free Syntheses, Configuration Determination, and Biological Evaluation against Hepatic Cancer Stem Cells

<p>Role of Focal Adhesion Kinase in Head and Neck Squamous Cell Carcinoma and Its Therapeutic Prospect</p>

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