Artemisiae Iwayomogii Herba Inhibits Growth, Motility, and the PI3K/AKT/mTOR Signaling Pathway in Hepatocellular Carcinoma Cells

Kim, Ju‐Young; Jung, Kyung Hee; Choi, Jin Gyu; Oh, Myung Sook; Hong, Sung Kyung

doi:10.1055/a-1167-4284

Cited by 5 publications

(5 citation statements)

References 31 publications

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“…After 4 weeks of feeding pubertal mice with different concentrations of lysine (0%, 0.025%, 0.05% and 0.1%) in drinking water, the total proteins of mammary gland were extracted. The PI3K/AKT/mTOR signalling pathway mainly participates in the proliferation, growth, motility, metabolism and other physiological activities in response to extracellular stimuli (Kim et al, 2020;Sharma et al, 2017). In this study, we found that lysine activated the PI3K/AKT/mTOR signalling pathway.…”

Section: Discussionsupporting

confidence: 51%

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Lysine stimulates the development of the murine mammary gland at puberty via PI3K/AKT/mTOR signalling axis

et al. 2022

Animal Physiology Nutrition

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Lysine is one of the essential amino acids. The effect of lysine on milk protein and milk fat anabolism has been reported, but the effect on mammary glands development has not been studied in detail. The normal development of the mammary glands at puberty is crucial to lactation of mammals. In this study, to explore the effect of lysine on mammary glands development, we fed different concentrations of lysine (0.025%, 0.05%, 0.1%) to pubertal mice and found that the addition of 0.1% lysine to drinking water significantly promoted mammary glands development. Furthermore, we treated mMECs (mouse mammary epithelial cells) with different concentrations of lysine (0, 0.2, 0.4, 0.6, 0.8 and 1 mM) to explore the underlying mechanism, and found that lysine promoted the proliferation of mMECs and development of mammary glands through PI3K/AKT/mTOR signalling pathway in pubertal mice. Overall, the results of this study revealed that lysine activated the PI3K/AKT/mTOR signal axis, elevated protein concentrations of cell proliferation markers, such as PCNA, Cyclin D1 and D3, and enhanced the proliferation of mMECs, finally promoted the murine mammary glands development at puberty.

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Section: Discussionsupporting

confidence: 51%

“…The PI3K/AKT/mTOR signalling pathway mainly participates in the proliferation, growth, motility, metabolism and other physiological activities in response to extracellular stimuli (Kim et al, 2020; Sharma et al, 2017). In this study, we found that lysine activated the PI3K/AKT/mTOR signalling pathway.…”

Section: Discussionmentioning

confidence: 99%

Lysine stimulates the development of the murine mammary gland at puberty via PI3K/AKT/mTOR signalling axis

et al. 2022

Animal Physiology Nutrition

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“…Besides, accumulating evidences have suggested the participation of the activated PI3K/Akt pathway in the growth-promoting effects of PTEN in HCC [ 19 – 22 ]. The blockade of the PI3K/AKT/mTOR pathway can help efficiently induce apoptosis and inhibit the growth, migration, and invasion of human HCC cells [ 23 ]. Likewise, in our study, high expression of PI3K was also observed in HCC tissues and delivery of a lentiviral vector containing human PTEN exerted inhibitory effects on HCC cell malignant behaviors while inducing apoptosis by inhibiting the PI3K/Akt pathway.…”

Section: Discussionmentioning

confidence: 99%

Loss of PTEN expression is associated with PI3K pathway-dependent metabolic reprogramming in hepatocellular carcinoma

et al. 2020

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Background: Metabolic reprogramming, in which energetic metabolism changes from oxidative phosphorylation to glycolysis, is well-accepted as a hallmark of cancers including hepatocellular carcinoma (HCC). A growing body of evidence suggests the involvement of oncogenes and tumor suppressor genes in the control of metabolic reprogramming. In this study, we attempt to investigate whether loss of PTEN, a recognized tumor suppressor, drives metabolic reprogramming of HCC. Methods: Cancerous liver tissues were surgically resected from 128 HCC patients, with 43 adjacent noncancerous liver tissues as control. Aerobic glycolysis (Warburg effect) was reflected by measurements of glucose uptake and lactate production, mitochondrial membrane potential collapse was observed by JC-1 staining, glycolytic rate and mitochondrial respiration were evaluated by determining glycolytic proton efflux rate (glycoPER) and oxygen consumption rate (OCR) in cultured human HHCC cells. Results: Reciprocal expression of PTEN and PI3K was determined in cancer liver tissues. Overexpression of PTEN suppressed the Warburg effect, as evidenced by reductions in glucose uptake and lactate production, maintenance of mitochondrial function, and transformation of energetic metabolism from glycolysis to oxidative phosphorylation in cultured PTEN-negative HHCC cells. Importantly, 740 Y-P, a PI3K agonist that leads to activation of the PI3K pathway, partially abrogated the function of PTEN and reprogramed glucose metabolism in cultured HHCC cells. Conclusions: The discovery that loss of PTEN allows the tumor metabolic program has been a major advance in understanding the carcinogenesis of HCC.

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“…Additionally, HCC is intrinsically resistant to a number of cytotoxic agents. Natural products are generally considered as safe supplier for biomedical applications due to their low toxicity ( Kim et al, 2020 ). In cancer therapy, naturally derived agents represent the largest portion of approved anti-tumor drugs ( Newman and Cragg, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Artemisia argyi Essential Oil Inhibits Hepatocellular Carcinoma Metastasis via Suppression of DEPDC1 Dependent Wnt/β-Catenin Signaling Pathway

Tian

Zhong

et al. 2021

Front. Cell Dev. Biol.

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The tumor metastasis is the major hurdle for the treatment of advanced hepatocellular carcinoma (HCC), due in part to the lack of effective systemic treatments. DEPDC1, a novel oncoantigen upregulated in HCC, is thought to be a molecular-target for novel therapeutic drugs. Artemisia argyi is a traditional Chinese medicine with anti-inflammatory and anti-tumor activities. This study investigated the potential therapeutic benefits of Artemisia argyi essential oil (AAEO) in suppressing metastasis of HCC by targeting DEPDC1. Assessment of AAEO cytotoxicity was performed by MTT assay. Anti-metastatic effects of AAEO were investigated in vitro using wound healing and transwell assays. The HepG2 cells were transduced with lentiviral vector containing luciferase (Luc). A metastasis model of nude mice was established by tail vein injection of HepG2-Luc cells. The nude mice were treated with AAEO (57.5, 115, and 230 mg/kg) or sorafenib (40 mg/kg). Metastasis of HCC cells was monitored via in vivo bioluminescence imaging. After treatment for 21 days, tissues were collected for histological examination and immunohistochemistry analysis. Gene and protein levels were determined by real-time quantitative PCR and western blotting. The results revealed that AAEO significantly inhibits the migration and invasion in vitro in a concentration-dependent manner. In vivo assays further confirmed that AAEO markedly inhibits HCC metastasis into lung, brain, and femur tissues and exhibits low toxicity. Our results suggested that AAEO significantly downregulates the mRNA and protein expression of DEPDC1. Also, AAEO attenuated Wnt/β-catenin signaling through reduction of Wnt1 and β-catenin production. Moreover, AAEO prevented epithelial-mesenchymal transition (EMT) by downregulation of vimentin and upregulation of E-cadherin. Furthermore, we found that DEPDC1 promoted HCC migration and invasion via Wnt/β-catenin signaling pathway and EMT. These results demonstrate that AAEO effectively inhibits HCC metastasis via attenuating Wnt/β-catenin signaling and inhibiting EMT by suppressing DEPDC1 expression. Thus, AAEO likely acts as a novel inhibitor of the DEPDC1 dependent Wnt/β-catenin signaling pathway.

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Artemisiae Iwayomogii Herba Inhibits Growth, Motility, and the PI3K/AKT/mTOR Signaling Pathway in Hepatocellular Carcinoma Cells

Cited by 5 publications

References 31 publications

Lysine stimulates the development of the murine mammary gland at puberty via PI3K/AKT/mTOR signalling axis

Lysine stimulates the development of the murine mammary gland at puberty via PI3K/AKT/mTOR signalling axis

Loss of PTEN expression is associated with PI3K pathway-dependent metabolic reprogramming in hepatocellular carcinoma

Artemisia argyi Essential Oil Inhibits Hepatocellular Carcinoma Metastasis via Suppression of DEPDC1 Dependent Wnt/β-Catenin Signaling Pathway

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