Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway

Yang, Lehe; Zhu, Tianru; Ye, Hua; Shen, Yili; Li, Zhiping; Chen, Luye; Wang, Canwei; Chen, Xia; Zhao, Haiyang; Xiang, Youqun; Xiao, Zhifeng; Zhao, Chengguang; Li, Jifa; Hu, Wanle

doi:10.1111/jcmm.16134

Cited by 15 publications

(11 citation statements)

References 34 publications

(79 reference statements)

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“…At the same time, we found that the paclitaxel-treated mice died or became emaciated in the late treatment period, whereas the gracillin-treated mice did not. From the H&E staining results of liver, lung, heart, and kidney of mice, it can be found that gracillin is basically non-toxic to mice, and literature reports can also prove this result ( 24 ). Study on the anti-tumor mechanism, absorption, and metabolism of gracillin in vivo will become the direction of our future research.…”

Section: Discussionmentioning

confidence: 87%

“…Chen found that gracillin induces human leukemia HL60 cell apoptosis and cell cycle G1 block via oxidative stress pathway ( 21 ); Min found that gracillin disrupts complex II-mediated mitochondrial function by inactivating succinate dehydrogenase, which resulted in decreased mitochondrial membrane potential, oxidative phosphorylation, and ATP production, at the same time, increased mitochondrial ROS production ( 22 ). And then they found that gracillin exerts a powerful anti-tumor effect mainly by inhibiting the production of bioenergy mediated by glycolysis and oxidative phosphorylation in tumor cells ( 23 ).Yang found that Gracillin exhibits a powerful anti-colorectal cancer effect by inhibiting the STAT3 pathway ( 24 ). The anti-tumor potential of gracillin is obvious, but there are relatively few studies on anti-tumor mechanisms, mainly involving apoptosis and energy metabolism.…”

Section: Introductionmentioning

confidence: 99%

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Gracillin Shows Potential Efficacy Against Non-Small Cell Lung Cancer Through Inhibiting the mTOR Pathway

Liu

et al. 2022

Front. Oncol.

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The leading cause of cancer deaths is lung cancer, non-small cell lung cancer (NSCLC), the most common type of lung cancers, remains a difficult cancer to treat and cure. It is urgent to develop new products to treat NSCLS. Gracillin, extracted from Reineckia carnea, Dioscorea villosa, and other medicinal plants, has anti-tumor potential with toxic effect on a variety of tumor cells such as NSCLC. However, the anti-NSCLC mechanism of gracillin is not completely clear. In this study, A549 cells and athymic nude mice were used as models to evaluate the anti-NSCLC effects of gracillin. The antiproliferative activity of gracillin on A549 cells was conducted by CCK-8, and obvious autophagy was observed in gracillin-treated A549 through transmission electron microscopy. Furthermore, the expressions of Beclin-1, LC3-II, and WIPI1 were upregulated, while the expression of p62 was downregulated in gracillin-treated A549. The further mechanism study found that the mTOR signaling pathway was significantly inhibited by gracillin. Accordingly, the PI3K/Akt pathway positively regulating mTOR was inhibited, and AMPK negatively regulating mTOR was activated. Meanwhile, LC3-II transformation was found to be significantly reduced after WIPI1 was silenced in A549 cells but increased after gracillin treatment. It also proves that WIPI is involved in the process of gracillin regulating A549 autophagy. At last, the anti-tumor growth activity of gracillin in vivo was validated in A549-bearing athymic nude mice. In conclusion, gracillin has anti-NSCLC activity by inducing autophagy. The mechanism maybe that gracillin inhibited the mTOR signaling pathway. Gracillin has the potential to be a candidate product for the treatment of NSCLC in the future.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Gracillin Shows Potential Efficacy Against Non-Small Cell Lung Cancer Through Inhibiting the mTOR Pathway

Liu

et al. 2022

Front. Oncol.

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“…Drug targets of the active ingredients in Chonglou (dioscin ( Tao et al, 2018 ; Ding et al, 2020 ; Wu et al, 2020 ), gracillin ( Liu et al, 2021 ; Yang J. et al, 2021 ; Yang L. et al, 2021 ), polyphyllin I ( Chang et al, 2017 ; Tian et al, 2020 ; Lai et al, 2021 ; Shen et al, 2021 ), polyphyllin II ( Niu et al, 2020 ), polyphyllin III ( Zhou et al, 2021 ), polyphyllin VI ( Liu et al, 2020 ; Teng et al, 2020 ), polyphyllin VII ( He et al, 2020 ; Zhao et al, 2021 ) and polyphyllin H) were collected by using the online tools ( Su et al, 2019 ), including PubChem ( https://pubchem.ncbi.nlm.nih.gov/ ), Swiss Target Prediction ( http://www.swisstargetprediction.ch/index.php ) and TargetNet ( http://targetnet.scbdd.com/home/index/ ).…”

Section: Methodsmentioning

confidence: 99%

Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes

Zhao

Zhao²,

Chang³

et al. 2023

Front. Genet.

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Lung adenocarcinoma (LUAD) is the main histological type of lung cancer with an unfavorable survival rate. Metastasis is the leading LUAD-related death with Epithelial-Mesenchymal Transition (EMT) playing an essential role. The anticancer efficacies of the active ingredients in Chonglou have been widely reported in various cancers. However, the potential therapeutic targets of the Chonglou active ingredients in LUAD patients remain unknown. Here, the network pharmacology and bioinformatics were performed to analyze the associations of the clinical characteristics, immune infiltration factors and m6A-related genes with the EMT-related genes associated with LUAD (EMT-LUAD related genes), and the molecular docking, STRING, GO, and KEGG enrichment for the drug targets of Chonglou active ingredients associated with EMT (EMT-LUAD-Chonglou related genes). And, cell viability analysis and cell invasion and infiltration analysis were used to confirm the theoretical basis of this study. A total of 166 EMT-LUAD related genes were identified and a multivariate Cox proportional hazards regression model with a favorable predictive accuracy was constructed. Meanwhile, the immune cell infiltration, immune cell subsets, checkpoint inhibitors and the expression of m6A-related genes were significantly associated with the risk scores for EMT-LUAD related genes with independent significant prognostic value of all included LUAD patients. Furthermore, 12 EMT-LUAD-Chonglou related genes with five core drug targets were identified, which participated in LUAD development through extracellular matrix disassembly, collagen metabolic process, collagen catabolic process, extracellular matrix organization, extracellular structure organization and inflammatory response. Moreover, we found that the active ingredients of Chonglou could indeed inhibit the progression of lung adenocarcinoma cells. These results are oriented towards EMT-related genes to achieve a better understanding of the role of Chonglou and its targets in osteosarcoma development and metastasis, thus guiding future preclinical studies and facilitating clinical translation of LUAD treatment.

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“…[62] The other sources of gracillin include Aconitum carmichaeli, [63] Costus speciosus, [64] Paris polyphylla Smith var. yunnanensis, [65] Reineckia carnea, [66] and Rhizoma paridis. [67] Various studies state that all these plants have anticancer properties along with other therapeutic benefits [65,[68][69][70][71] (Table 1).…”

Section: Botanical Sources Of Gracillinmentioning

confidence: 99%

Anticancer Potential of the Plant‐Derived Saponin Gracillin: A Comprehensive Review of Mechanistic Approaches

Bhuia,

Chowdhury,

Sonia

et al. 2023

Chemistry & Biodiversity

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With the increasing prevalence of cancer and the toxic side effects of synthetic drugs, natural products are being developed as promising therapeutic approaches. Gracillin is a naturally occurring triterpenoid steroidal saponin with several therapeutic activities. It is obtained as a major compound from different Dioscorea species. This review was designated to summarize the research progress on the anti‐cancer activities of gracillin focusing on the underlying cellular and molecular mechanisms, as well as its pharmacokinetic features. The data were collected (up to date as of May 1, 2023) from various reliable and authentic literatures comprising PubMed, Springer Link, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. The findings demonstrated that gracillin displays promising anticancer effects through various molecular mechanisms, including anti‐inflammatory effects, apoptotic cell death, induction of oxidative stress, cytotoxicity, induction of genotoxicity, cell cycle arrest, anti‐proliferative effect, autophagy, inhibition of glycolysis, and blocking of cancer cell migration. Additionally, this review highlighted the pharmacokinetic features of gracillin, indicating its lower oral bioavailability. As a conclusion, it can be proposed that gracillin could serve as a hopeful chemotherapeutic agent. However, further extensive clinical research is recommended to establish its safety, efficacy, and therapeutic potential in cancer treatment.

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Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 15 publications

References 34 publications

Gracillin Shows Potential Efficacy Against Non-Small Cell Lung Cancer Through Inhibiting the mTOR Pathway

Gracillin Shows Potential Efficacy Against Non-Small Cell Lung Cancer Through Inhibiting the mTOR Pathway

Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes

Anticancer Potential of the Plant‐Derived Saponin Gracillin: A Comprehensive Review of Mechanistic Approaches

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