Traditional Chinese medicine formula <scp>T33</scp> inhibits the proliferation of human colorectal cancer cells by inducing autophagy

Liu, Yu‐Te; Tzang, Bor‐Show; Yow, Jia-Le; Chiang, Yi‐Hsuan; Huang, Chih‐Yang; Hsu, Tsai‐Ching

doi:10.1002/tox.23460

Cited by 19 publications

(9 citation statements)

References 58 publications

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“…Such as inhibition of autophagy leading to regression of pancreatic cancer ( 66 ) and lung cancer ( 67 ) suggests a role for autophagy in sustaining tumor growth. While the induction of autophagy in renal cell cancer ( 68 ), colorectal cancer ( 69 ) inhibits cell proliferation, suggesting that excessive autophagy can limit cell growth. Our data and others suggest that significant deviations from the physiological set point of basal autophagy, either high or low, can lead to cellular toxicity.…”

Section: Discussionmentioning

confidence: 99%

RAC3 Inhibition Induces Autophagy to Impair Metastasis in Bladder Cancer Cells via the PI3K/AKT/mTOR Pathway

Wang

Shi

et al. 2022

Front. Oncol.

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BackgroundBladder cancer (BCa) is one of the most frequent malignant tumors globally, with a significant morbidity and mortality rate. Gene expression dysregulation has been proven to play a critical role in tumorigenesis. Ras-related C3 botulinum toxin substrate3 (RAC3), which is overexpressed in several malignancies and promotes tumor progression, has been identified as an oncogene. However, RAC3 has important but not fully understood biological functions in cancer. Our research aims to reveal the new functions and potential mechanisms of RAC3 involved in BCa progression.MethodsWe explored the expression level of RAC3 and its relationship with prognosis by publicly accessible BCa datasets, while the correlation of RAC3 expression with clinicopathological variables of patients was analyzed. In vitro and in vivo proliferation, migration, autophagy, and other phenotypic changes were examined by constructing knockdown(KD)/overexpression(OE) RAC3 cells and their association with PI3K/AKT/mTOR pathway was explored by adding autophagy-related compounds.ResultsCompared with non-tumor samples, RAC3 was highly expressed in BCa and negatively correlated with prognosis. KD/OE RAC3 inhibited/promoted the proliferation and migration of BCa cells. Knockdown RAC3 caused cell cycle arrest and decreased adhesion without affecting apoptosis. Inhibition of RAC3 activates PI3K/AKT/mTOR mediated autophagy and inhibits proliferation and migration of BCa cells in vivo and in vitro. Autophagy inhibitor 3MA can partially rescue the metastasis and proliferation inhibition effect caused by RAC3 inhibition. Inhibit/activate mTOR enhanced/impaired autophagy, resulting in shRAC3-mediated migration defect exacerbated/rescued.ConclusionRAC3 is highly expressed in BCa. It is associated with advanced clinicopathological variables and poor prognosis. Knockdown RAC3 exerts an antitumor effect by enhancing PI3K/AKT/mTOR mediated autophagy. Targeting RAC3 and autophagy simultaneously is a potential therapeutic strategy for inhibiting BCa progression and prolonging survival.

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Section: Discussionmentioning

confidence: 99%

RAC3 Inhibition Induces Autophagy to Impair Metastasis in Bladder Cancer Cells via the PI3K/AKT/mTOR Pathway

Wang

Shi

et al. 2022

Front. Oncol.

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“…Noteworthy is the immune-enhancement effect of CH [ 70 , 71 ], which maintains the functional gut immunity for necessary pathogen recognition and elimination. Complications: ① a broad array of investigations have reported the antitumor effect of BT [ 72 ], PP [ 73 ], BD [ 74 – 76 ], CH [ 77 , 78 ], LC [ 79 , 80 ], SK [ 81 – 83 ], and CWT [ 84 , 85 ], which is considered a major complication of UC. Based on TCGA database, the targets of JW clustered COAD patients into two groups and correlated with the survival probability.…”

Section: Discussionmentioning

confidence: 99%

“…Complications: ① a broad array of investigations have reported the antitumor effect of BT [ 72 ], PP [ 73 ], BD [ 74 – 76 ], CH [ 77 , 78 ], LC [ 79 , 80 ], SK [ 81 – 83 ], and CWT [ 84 , 85 ], which is considered a major complication of UC. Based on TCGA database, the targets of JW clustered COAD patients into two groups and correlated with the survival probability.…”

Section: Discussionmentioning

confidence: 99%

Validation of the Anticolitis Efficacy of the Jian-Wei-Yu-Yang Formula

Yan

Tang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Inflammatory bowel disease (IBD) is a major cause of morbidity and mortality due to its repetitive remission and relapse. The Jian-Wei-Yu-Yang (JW) formula has a historical application in the clinic to combat gastrointestinal disorders. The investigation aimed to explore the molecular and cellular mechanisms of JW. Methods. 2% dextran sodium sulfate (DSS) was diluted in drinking water and given to mice for 5 days to establish murine models of experimental colitis, and different doses of JW solution were administered for 14 days. Network pharmacology analysis and weighted gene co-expression network analysis (WGCNA) were utilized to predict the therapeutic role of JW against experimental colitis and colitis-associated colorectal cancer (CAC). 16S rRNA sequencing and untargeted metabolomics were conducted using murine feces. Western blotting, immunocytochemistry, and wound healing experiments were performed to confirm the molecular mechanisms. Results. (1) Liquid chromatography with mass spectrometry was utilized to confirm the validity of the JW formula. The high dose of JW treatment markedly attenuated DSS-induced experimental colitis progression, and the targets were enriched in inflammation, infection, and tumorigenesis. (2) The JW targets were related to the survival probability in patients with colorectal cancer, underlying a potential therapeutic value in CRC intervention. (3) Moreover, the JW therapy successfully rescued the decreased richness and diversity of microbiota, suppressed the potentially pathogenic phenotype of the gut microorganisms, and increased cytochrome P450 activity in murine colitis models. (4) Our in vitro experiments confirmed that the JW treatment suppressed caspase3-dependent pyroptosis, hypoxia-inducible factor 1α (HIF1α), and interleukin-1b (IL-1b) in the colon; facilitated the alternative activation of macrophages (Mφs); and inhibited tumor necrosis factor-α (TNFα)-induced reactive oxygen species (ROS) level in intestinal organoids (IOs). Conclusion. The JW capsule attenuated the progression of murine colitis by a prompt resolution of inflammation and bloody stool and by re-establishing a microbiome profile that favors re-epithelization and prevents carcinogenesis.

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“…Accumulating evidence indicated that melatonin, 11 dichlorodiphenyltrichloroethane, 12 xiaotansanjiefang, 13 traditional Chinese medicine formula T33, 14 and some active ingredients and extracts of traditional Chinese medicine, such as xanthohumol, 15 hinokitiol, 16 bergapten, 17 lupeol, 18 tribulus terrestris fruit extract, 19 momordica balsamina crude acetone extract, 20 and crude extract of Rheum palmatum L 21,22 showed the anti‐cancer activity in colorectal cancer. In addition, the leguminous plant sophora flavescens has been used for more than 2000 years, as a traditional Chinese medicine, and matrine, an alkaloid, was extracted from it and exerted multiple pharmacological effects, such as antiviral, diuretic, anti‐inflammatory and anti‐allergic effects 23,24 .…”

Section: Introductionmentioning

confidence: 99%

Matrine restrains the development of colorectal cancer through regulating the AGRN/Wnt/β‐catenin pathway

Wen

et al. 2023

Environmental Toxicology

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Background Colorectal cancer is a common malignant digestive tract tumor. This study aimed to explore the biological role and potential underlying mechanism of matrine in colorectal cancer. Methods The mRNA expression of AGRN was measured using RT‐qPCR. Cell proliferation, migration, invasion and apoptosis were determined using CCK‐8, EdU, transwell assays and flow cytometry, respectively. Xenograft tumor experiment was performed to explore the action of matrine and AGRN on tumor growth in colorectal cancer in vivo. Immunohistochemistry (IHC) assay was applied for AGRN, β‐catenin, and c‐Myc expression in the tumor tissues from mice. Results Matrine dramatically repressed cell growth and reduced the level of AGRN in colorectal cancer cells. AGRN expression was boosted colorectal cancer tissues and cells. AGRN downregulation depressed cell proliferation, migration, invasion, and enhanced cell apoptosis in colorectal cancer cells. Moreover, matrine showed the anti‐tumor effects on colorectal cancer cells via regulating AGRN expression. AGRN knockdown could inactivate the Wnt/β‐catenin pathway in colorectal cancer cells. We found that AGRN downregulation exhibited the inhibition action in the progression of colorectal cancer by modulating the Wnt/β‐catenin pathway. In addition, matrine could inhibit the activation of the Wnt/β‐catenin pathway through regulating AGRN in colorectal cancer cells. Furthermore, xenograft tumor experiment revealed that matrine treatment or AGRN knockdown repressed the development of colorectal cancer via the Wnt/β‐catenin pathway in vivo. Conclusion Matrine retarded colorectal cancer development by modulating AGRN to inactivate the Wnt/β‐catenin pathway.

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Traditional Chinese medicine formula T33 inhibits the proliferation of human colorectal cancer cells by inducing autophagy

Cited by 19 publications

References 58 publications

RAC3 Inhibition Induces Autophagy to Impair Metastasis in Bladder Cancer Cells via the PI3K/AKT/mTOR Pathway

RAC3 Inhibition Induces Autophagy to Impair Metastasis in Bladder Cancer Cells via the PI3K/AKT/mTOR Pathway

Validation of the Anticolitis Efficacy of the Jian-Wei-Yu-Yang Formula

Matrine restrains the development of colorectal cancer through regulating the AGRN/Wnt/β‐catenin pathway

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