Atractylenolide I inhibits colorectal cancer cell proliferation by affecting metabolism and stemness via AKT/mTOR signaling

Wang, Kuilong; Huang, Wei; Sang, Xianan; Wu, Xing-Zheng; Shan, Qiyuan; Tang, Dongdong; Xu, Xiaojuan; Cao, Gang

doi:10.1016/j.phymed.2020.153191

Cited by 44 publications

(36 citation statements)

References 28 publications

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“…Other factors of plant origin acting on glucose metabolism in CRC cells include Atractylenolide I (ATL-1). This compound is an eudesmane-type sesquiterpenoid lactone derivative of Rhizoma Atractylodis macrocephalae, known in traditional Chinese medicine [ 242 , 243 ]. In addition to inhibiting CRC cell invasion and inducing their apoptosis, ATL-1 also alters glucose metabolism, and suppressed stem-like traits.…”

Section: Therapeutic Strategies For Reduction Of Metabolic Glucose Disorders In Crcmentioning

confidence: 99%

“…It acts as an ACT/mTOR signaling inhibitor by lowering the phosphorylation of proteins associated with this pathway. In vivo studies have shown a reduction in tumor weight and volume and confirmed impaired aerobic glycolysis, stemness maintenance and Akt/mTOR activation in colorectal tumors [ 242 ]. Other studies have confirmed that ATL-1 anticancer activity in CRC is associated with apoptosis induction and glycolysis suppression in CRC cells through inhibition of Janus kinase 2 (JAK2)/STAT3 signaling.…”

Section: Therapeutic Strategies For Reduction Of Metabolic Glucose Disorders In Crcmentioning

confidence: 99%

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Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer

Kasprzak

2021

IJMS

101

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Colorectal cancer (CRC) is one of the most common aggressive carcinoma types worldwide, characterized by unfavorable curative effect and poor prognosis. Epidemiological data re-vealed that CRC risk is increased in patients with metabolic syndrome (MetS) and its serum components (e.g., hyperglycemia). High glycemic index diets, which chronically raise post-prandial blood glucose, may at least in part increase colon cancer risk via the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. Hyperactivated glucose uptake and aerobic glycolysis (the Warburg effect) are considered as a one of six hallmarks of cancer, including CRC. However, the role of insulin/IGF-1 signaling during the acquisition of the Warburg metabolic phenotypes by CRC cells is still poorly understood. It most likely results from the interaction of multiple processes, directly or indirectly regulated by IGF-1, such as activation of PI3K/Akt/mTORC, and Raf/MAPK signaling pathways, activation of glucose transporters (e.g., GLUT1), activation of key glycolytic enzymes (e.g., LDHA, LDH5, HK II, and PFKFB3), aberrant expression of the oncogenes (e.g., MYC, and KRAS) and/or overexpression of signaling proteins (e.g., HIF-1, TGF-β1, PI3K, ERK, Akt, and mTOR). This review describes the role of IGF-1 in glucose metabolism in physiology and colorectal carcinogenesis, including the role of the insulin/IGF system in the Warburg effect. Furthermore, current therapeutic strategies aimed at repairing impaired glucose metabolism in CRC are indicated.

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Section: Therapeutic Strategies For Reduction Of Metabolic Glucose Disorders In Crcmentioning

confidence: 99%

Section: Therapeutic Strategies For Reduction Of Metabolic Glucose Disorders In Crcmentioning

confidence: 99%

Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer

Kasprzak

2021

IJMS

101

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“…ATL-1 (25–75 mg/kg) downregulated the Akt/mTOR pathway and altered the glucose metabolism and stem-like behavior in colon cancer cells. It also inhibited the colorectal tumor progression in xenografted nude mice [ 43 ]. The total polyphenolic fractions obtained from Fructus viticis were shown to modulate the Akt/mTOR pathway and repressed the stemness characteristics in lung CSCs [ 44 ].…”

Section: Phytomedicines Targeting Key Regulators Of Anti-cancer Drug Resistance In Cscsmentioning

confidence: 99%

Phytomedicines Targeting Cancer Stem Cells: Therapeutic Opportunities and Prospects for Pharmaceutical Development

et al. 2021

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The presence of small subpopulations of cells within tumor cells are known as cancer stem cells (CSCs). These cells have been the reason for metastasis, resistance with chemotherapy or radiotherapy, and tumor relapse in several types of cancers. CSCs underwent to epithelial–mesenchymal transition (EMT) and resulted in the development of aggressive tumors. CSCs have potential to modulate numerous signaling pathways including Wnt, Hh, and Notch, therefore increasing the stem-like characteristics of cancer cells. The raised expression of drug efflux pump and suppression of apoptosis has shown increased resistance with anti-cancer drugs. Among many agents which were shown to modulate these, the plant-derived bioactive agents appear to modulate these key regulators and were shown to remove CSCs. This review aims to comprehensively scrutinize the preclinical and clinical studies demonstrating the effects of phytocompounds on CSCs isolated from various tumors. Based on the available convincing literature from preclinical studies, with some clinical data, it is apparent that selective targeting of CSCs with plants, plant preparations, and plant-derived bioactive compounds, termed phytochemicals, may be a promising strategy for the treatment of relapsed cancers.

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“…Baizhu, or Atractylodes macrocephala Koidz, is a dry perennial rhizome in the Asteraceae family and has been applied as a typical component of many traditional Chinese medical formulations. 12,13 Among the components of baizhu, three forms of atractylenolides (ATLs) (I, II, and III) have been identified to exert pharmacological properties, and ATL-1 is the main active ingredient that has exhibited therapeutic effects against CRC. [14][15][16][17] Despite this, studies on ATL-1 in contemporary cancer treatment are scarce, as are those on its effects on CSCs and the dynamics of miR-carrying EVs.…”

Section: Introductionmentioning

confidence: 99%

“…Aside from conventional anticancer schemes such as surgical intervention and chemotherapy, natural herbal and plant‐based compounds have gained attention as adjuvant or complementary therapies in cancer treatment. Baizhu, or Atractylodes macrocephala Koidz, is a dry perennial rhizome in the Asteraceae family and has been applied as a typical component of many traditional Chinese medical formulations 12,13 . Among the components of baizhu, three forms of atractylenolides (ATLs) (I, II, and III) have been identified to exert pharmacological properties, and ATL‐1 is the main active ingredient that has exhibited therapeutic effects against CRC 14‐17 .…”

Section: Introductionmentioning

confidence: 99%

Transfer of metastatic traits via miR‐200c in extracellular vesicles derived from colorectal cancer stem cells is inhibited by atractylenolide I

Tang

Ying

et al. 2020

Clinical & Translational Med

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Cancer stem cells (CSCs) are important factors contributing to tumorigenesis. We examined whether CSCs isolated from colorectal cancer (CRC) cells possess metastatic properties that can be transferred to non‐CSCs via the delivery of miR‐200c enclosed in extracellular vesicles (EVs). The inhibitory effect of atractylenolide I (ATL‐1), a traditional Chinese medicinal compound, on miR‐200c activity and metastatic transfer was investigated. EVs were isolated from colorectal CSCs. The expression of miR‐200c was evaluated in CSCs and CSC‐derived EVs, and horizontal transfer of metastatic properties via EVs to non‐CSCs was investigated in terms of cell behavior and phosphatidylinositol‐4,5‐bisphosphate 3‐kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling. CSCs isolated from metastatic CRC cells exhibited higher levels of miR‐200c than those in nonmetastatic CRC cells. Overexpression of miR‐200c in CSCs enhanced metastatic potential by promoting proliferation and inhibiting apoptosis, in turn leading to the release of EVs carrying an excess of miR‐200c. Non‐CSCs co‐cultured with miR‐200c‐containing EVs exhibited enhanced invasion and stemness maintenance associated with PI3K/Akt/mTOR activation, demonstrating successful metastatic transfer via EV delivery. Furthermore, ATL‐1 impaired the EV‐mediated transfer of metastatic properties by suppressing miR‐200c activity and disrupting EV uptake by non‐CSCs. EVs are critical signal transducers that facilitate intercellular communication and exchange of metastatic properties, which can be controlled by ATL‐1. The findings are useful in the development of microRNA‐based anticancer strategies by targeting EV‐mediated activity, especially using natural compounds.

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Atractylenolide I inhibits colorectal cancer cell proliferation by affecting metabolism and stemness via AKT/mTOR signaling

Cited by 44 publications

References 28 publications

Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer

Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer

Phytomedicines Targeting Cancer Stem Cells: Therapeutic Opportunities and Prospects for Pharmaceutical Development

Transfer of metastatic traits via miR‐200c in extracellular vesicles derived from colorectal cancer stem cells is inhibited by atractylenolide I

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