Gaillardin, a potent sesquiterpene lactone induces apoptosis via down-regulation of NF‐κβ in gastric cancer cells, AGS and MKN45

Roozbehani, Maryam; Abdolmohammadi, Mohammad Hossein; Hamzeloo-Moghadam, Maryam; Irani, Shiva; Fallahian, Faranak

doi:10.1016/j.jep.2021.114529

Cited by 14 publications

(9 citation statements)

References 32 publications

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“…Some natural products, such as curcumin, resveratrol, artesunate, and gallic acid, exert anticancer effects by inducing cell apoptosis. Theranekron D6 (Tosun et al, 2021) obtained from spider venom and gaillardin (Roozbehani et al, 2021) isolated from Inula oculus-christi have attracted great attention due to their significant proapoptotic properties, and therefore, they may be powerful candidates for inducing apoptosis in the future. Camptothecin, curcumin (Rowaiye et al, 2021), isoquinoline alkaloids of Chelidonium majus (Noureini et al, 2017), amentoflavone (Revikumar, 2021), and emodin (Liu et al, 2019), are effective telomerase inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Research Status and Hotspots of Anticancer Natural Products Based on the Patent Literature and Scientific Articles

Shen

2022

Front. Pharmacol.

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Background: The patent literature contains a large amount of information on the internal state of current industrial technologies that are not available in other literature studies. Scientific articles are the direct achievements of theoretical research in this field and can reveal how current theories in basic research have developed. In this study, the progress and status of natural anticancer products in this field were summarized, and the research hotspots were explored through the analysis of the relevant patent literature and scientific articles.Methods: Patent data were retrieved from the incoPat patent retrieval database, and paper data were retrieved from the Web of Science core set and PubMed. GraphPad Prism 8, Microsoft Excel 2010, and CiteSpace 5.8.R3 were used to perform visual processing. The analyzed patent literature includes the patent applicant type, country (or region), and technical subject. The analyzed scientific article includes academic groups, subject areas, keyword clustering, and burst detection.Results: A total of 20,435 patent families and 38,746 articles were collected by 4 January 2022. At present, antitumor drugs derived from natural products mainly include 1) apoptosis inducers such as curcumin, gallic acid, resveratrol, Theranekron D6, and gaillardin; 2) topoisomerase inhibitors such as camptothecins, scaffold-hopped flavones, podophyllotoxin, oxocrebanine, and evodiamine derivatives; 3) telomerase inhibitors such as camptothecin and isoquinoline alkaloids of Chelidonium majus, amentoflavone, and emodin; 4) microtubule inhibitors such as kolaflavanone, tanshinone IIA analog, eugenol, and millepachine; 5) immunomodulators such as fucoidan, myricetin, bergapten, and atractylenolide I; 6) tumor microenvironment regulators such as beta-escin and icaritin; 7) multidrug resistance reversal agents such as berberine, quercetin, and dihydromyricetin; and 8) antiangiogenic and antimetastatic agents such as epigallocatechin-3-gallate, lupeol, ononin, and saikosaponin A.Conclusion: Anticancer natural product technology was introduced earlier, but the later development momentum was insufficient. In addition, scientific research activities are relatively closed, and technical exchanges need to be strengthened. Currently, the development of medicinal plants and the research on the anticancer mechanism of natural active products are still research hotspots, especially those related to immune checkpoints, essential oils, and metastatic cancer. Theories of traditional Chinese medicine (TCM), such as “restraining excessiveness to acquire harmony,” “same treatment for different diseases,” “Meridian induction theory,” and “Fuzheng Quxie,” have important guiding significance to the research of anticancer mechanisms and the development of new drugs and can provide new ideas for this process.Systematic Review Registration: [https://sourceforge.net/projects/citespace/], identifier [000755430500001].

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Section: Discussionmentioning

confidence: 99%

Research Status and Hotspots of Anticancer Natural Products Based on the Patent Literature and Scientific Articles

Shen

2022

Front. Pharmacol.

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“…As mentioned in previous studies, 20,21 Inula oculus‐christi L. with the voucher number (TMRC‐3312) was used to isolate GLN. In this process, the aerial parts of the powdered plant were extracted using chloroform, and components were separated by chromatographic methods.…”

Section: Methodsmentioning

confidence: 99%

“…Gaillardin (GLN), an Inula oculus‐christi ‐derived sesquiterpene lactone, exhibits remarkable cytotoxic effects on cancerous and leukaemic cells 20–23 . However, its efficacy on acute promyelocytic leukaemia remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

“…18 Gaillardin (GLN), an Inula oculus-christi-derived sesquiterpene lactone, exhibits remarkable cytotoxic effects on cancerous and leukaemic cells. [20][21][22][23] However, its efficacy on acute promyelocytic leukaemia remains poorly understood. Hence, we designed this study to explore the molecular mechanism of GLN and determine its effects on APL-derived HL-60 cells alone and in combination with ATO.…”

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confidence: 99%

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Gaillardin exerts potent antileukemic effects on HL‐60 cells and intensifies arsenic trioxide cytotoxicity: Providing new insight into sesquiterpene lactones in leukaemia treatment

Noormohamadi,

Hamzeloo‐Moghadam,

Bashash

et al. 2024

Clin Exp Pharma Physio

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The use of all‐trans retinoic acid and arsenic trioxide resulted in favourable therapeutic responses in standard‐risk acute promyelocytic leukaemia (APL) patients. However, resistance to these agents has made treating the high‐risk subgroup more problematic, and possible side effects limit their clinical dosages. Numerous studies have proven the cytotoxic properties of Gaillardin, one of the Inula oculus‐christi‐derived sesquiterpene lactones. Due to the adverse effects of arsenic trioxide on the high‐risk subgroup of APL patients, we aimed to assess the cytotoxic effect of Gaillardin on HL‐60 cells as a single or combined‐form approach. The results of the trypan blue and MTT assays outlined the potent cytotoxic properties of Gaillardin. The flow cytometric analysis and the mRNA expression levels revealed that Gaillardin attenuated the proliferative capacity of HL‐60 cells through cell cycle arrest and induced apoptosis via reactive oxygen species generation. Moreover, the results of synergistic experiments indicated that this sesquiterpene lactone sensitizes HL‐60 cells to the cytotoxic effects of arsenic trioxide. Taken together, the findings of the present investigation highlighted the antileukemic characteristics of Gaillardin by inducing G1 cell cycle arrest and triggering apoptosis. Gaillardin acts as an antileukemic metabolite against HL‐60 cells and this study provides new insight into treating APL patients, especially in the high‐risk subgroup.

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“…Metformin has been shown to promote apoptosis of MKN1, MKN45 and KATO-III cells by downregulating NF-κB signaling and has been shown to inhibit peritoneal metastasis in xenograft mouse models (Sekino et al, 2018). Gaillardin, an active small molecule derived from Inula oculus-christi, has recently been shown to induce apoptosis of AGS and MKN45 by downregulating NF-κB signaling pathway (Roozbehani et al, 2021). As a 3 0 '-O-methylated metabolite of quercetin, isorhamnetin can induce the apoptosis of AGS and MKN45 cells by inhibiting NF-κB signaling pathway and enhance the therapeutic effect of capeciatbine on xenograft mouse model (Manu et al, 2015).…”

Section: Compounds Targeting the Nf-κb Signaling Pathwaymentioning

confidence: 99%

Natural products targeting signaling pathways associated with regulated cell death in gastric cancer: Recent advances and perspectives

et al. 2023

Phytotherapy Research

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Gastric cancer (GC) is one of the most serious gastrointestinal malignancies with high morbidity and mortality. The complexity of GC process lies in the multi‐phenotypic linkage regulation, in which regulatory cell death (RCD) is the core link, which largely dominates the fate of GC cells and becomes a key determinant of GC development and prognosis. In recent years, increasing evidence has been reported that natural products can prevent and inhibit the development of GC by regulating RCDs, showing great therapeutic potential. In order to further clarify its key regulatory characteristics, this review focused on specific expressions of RCDs, combined with a variety of signaling pathways and their crosstalk characteristics, sorted out the key targets and action rules of natural products targeting RCD. It is highlighted that a variety of core biological pathways and core targets are involved in the decision of GC cell fate, including the PI3K/Akt signaling pathway, MAPK‐related signaling pathways, p53 signaling pathway, ER stress, Caspase‐8, gasdermin D (GSDMD), and so on. Moreover, natural products target the crosstalk of different RCDs by modulating above signaling pathways. Taken together, these findings suggest that targeting various RCDs in GC with natural products is a promising strategy, providing a reference for further clarifying the molecular mechanism of natural products treating GC, which warrants further investigations in this area.

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Gaillardin, a potent sesquiterpene lactone induces apoptosis via down-regulation of NF‐κβ in gastric cancer cells, AGS and MKN45

Cited by 14 publications

References 32 publications

Research Status and Hotspots of Anticancer Natural Products Based on the Patent Literature and Scientific Articles

Research Status and Hotspots of Anticancer Natural Products Based on the Patent Literature and Scientific Articles

Gaillardin exerts potent antileukemic effects on HL‐60 cells and intensifies arsenic trioxide cytotoxicity: Providing new insight into sesquiterpene lactones in leukaemia treatment

Natural products targeting signaling pathways associated with regulated cell death in gastric cancer: Recent advances and perspectives

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