scholarly journals Oleanolic Acid Induces Autophagy and Apoptosis via the AMPK-mTOR Signaling Pathway in Colon Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Changxiao Hu ◽  
Yibo Cao ◽  
Ping Li ◽  
Xiaorong Tang ◽  
Minhui Yang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Signaling Pathway ◽  
Oleanolic Acid ◽  
Mtor Signaling ◽  
Dependent Manner ◽  
Biological Functions ◽  
Mtor Signaling Pathway ◽  
Ampk Signaling ◽  
Apoptosis Rate ◽  
Hct 116

Aims. The purpose of this study was to explore the biological functions of the mTOR and AMPK signaling pathways in colon cancer (CC). The potential molecular mechanisms by which oleanolic acid (OA) induces autophagy and apoptosis were also investigated. Methods. The biological functions of mTOR were analyzed by GeneCards, the Search Tool for the Retrieval of Interacting Genes (STRING), and the Database for Annotation, Visualization and Integrated Discovery (DAVID). Least absolute shrinkage and selection operator (LASSO) regression analysis was used to obtain prognostic and survival data of CC patients from the Gene Expression Omnibus (GEO) database. The effects of OA on the CC cell lines HCT-116 and SW-480 were analyzed by CCK-8, colony formation assay, and high-content system (HCS) array scan. The apoptosis rate of SW-480 and HCT-116 cells was detected by flow cytometry. The mRNA and protein expression levels in HCT-116 and SW-480 cells and NCM-460 normal colonic epithelial cells were detected by RT-PCR and Western blotting. Results. mTOR was highly expressed in CC patients and acted as an oncogene. The AMPK signaling pathway mediated by mTOR predicted the poor prognosis of CC patients. OA effectively inhibited the proliferation and viability of CC cells. Furthermore, the apoptosis rate of CC cells was clearly increased following OA administration. Regarding the molecular mechanism of OA, the results indicated that mTOR and the antiapoptosis gene Bcl-2 were downregulated by OA. In addition, regulator genes of autophagy and apoptosis, including BAX, caspase-9, caspase-8, and caspase-3, were significantly upregulated by OA. Moreover, OA upregulated AMPK and its downstream proteins, including TSC2, BAX, Beclin 1, LC3B-II, and ULK1, to induce autophagy and apoptosis in CC cells. Conclusion. The findings from this study demonstrate that OA could effectively inhibit the proliferation and viability of CC cells. The anti-CC activity of OA is closely related to the activation of the AMPK-mTOR signaling pathway. Activation of AMPK and inhibition of mTOR are involved in the induction of autophagy and apoptosis by OA. OA induced autophagy and apoptosis mainly in an AMPK activation-dependent manner in CC cells.

scholarly journals Neogambogic acid induces apoptosis of melanoma B16 cells via the PI3K/Akt/mTOR signaling pathway

2020 ◽  
Author(s):  
Chunlan Wu ◽  
Jin He ◽  
Zhimin Sun ◽  
Dongxin Tang ◽  
Changhui Wen
Keyword(s):  
Signaling Pathway ◽  
Acid Concentration ◽  
Mtor Signaling ◽  
Dependent Manner ◽  
Proliferation Inhibition ◽  
Inhibition Rate ◽  
Mtor Signaling Pathway ◽  
Apoptosis Rate ◽  
Melanoma B16 ◽  
And Migration

Background: Neogambogic acid, as one of the main components of gamboge, exhibits high activities against various tumors. Objective: To explore the mechanism by which melanoma B16 cell apoptosis was induced by neogambogic acid. Methods: Melanoma B16 cells were treated with different concentrations of neogambogic acid solutions (0, 1.5, 3.0, 6.0 μM). The proliferation inhibition rate was measured by MTT assay. Cell morphology was observed by inverted microscope. Cell migration and invasion were tested by Transwell assay. Flow cytometry was performed to detect the apoptosis rate and cell cycle of B16 cells. The expressions of PI3K/Akt/mTOR signaling pathway-related proteins were detected by Western blot. Results: The proliferation inhibition rate of B16 cells significantly increased with rising neogambogic acid concentration (P<0.05). The invasive and migration capacities of B16 cells decreased significantly after treatment with neogambogic acid (P<0.05). The apoptosis rate also increased with rising concentration of neogambogic acid. After 24 h of treatment, the percentage of G0/G1 phase cells increased gradually as the neogambogic acid concentration rose, whereas those of S phase and G2/M phase cells decreased. With increasing concentration of neogambogic acid, the expressions of p-PI3K, p-Akt and p-mTOR proteins reduced in a time-dependent manner, but those of PI3K and Akt proteins remained basically unchanged. Conclusion: Neogambogic acid can inhibit the proliferation, invasion and migration of melanoma B16 cells and induce their apoptosis, which may be regulated via the PI3K/Akt/mTOR signaling pathway.

Active vitamin D activates chondrocyte autophagy to reduce osteoarthritis via mediating the AMPK–mTOR signaling pathway

2020 ◽  
Vol 98 (3) ◽  
pp. 434-442 ◽  
Author(s):  
Chunyu Kong ◽  
Changlei Wang ◽  
Yuquan Shi ◽  
Lei Yan ◽  
Junhua Xu ◽  
...  
Keyword(s):  
Vitamin D ◽  
Signaling Pathway ◽  
Therapeutic Option ◽  
Serum Levels ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Ampk Signaling ◽  
Hydroxyvitamin D ◽  
Compound C ◽  
Safranin O

Osteoarthritis (OA) is a common joint degenerative disease. Vitamin D (VD) is essential for bone health. We hypothesized that active VD could be used as a therapeutic treatment for OA. Low serum levels of 25-hydroxyvitamin D [25(OH)D] have been found in patients with OA, and thus the serum level of VD could be diagnostic of OA. To test this, we established a mouse model of OA. The results from staining with hematoxylin–eosin and Safranin O – Fast Green indicated that active VD reduced the symptoms of OA in mice. The results from Western blotting indicated that treatment with VD increased the activity of the p-AMPK–AMPK signaling pathway and decreased the p-mTOR–mTOR pathway; it also increased the ratio of LC3II:LC3I antibodies and the protein expression levels of Beclin-1, but decreased the level of p62. Further, treatment with VD reduced the levels of tumor necrosis factor-α and interleukin-6 both in cartilage tissues and in chondrocytes. Administration of the AMPK inhibitor compound C and autophagy inhibitor 3-methyladenine (3-MA) reversed these changes following VD treatment. In addition, the results from transfection with mRFP-GFP-LC3 indicated that active VD led to autophagosome aggregation in OA chondrocytes. 3-MA inhibited cell autophagy and promoted inflammation in OA. This study provides evidence that active VD activate chondrocyte autophagy to reduce OA inflammation via activating the AMPK–mTOR signaling pathway. Treatment with active VD could be a novel therapeutic option for OA.

scholarly journals Tandutinib Inhibits the Akt/mTOR Signaling Pathway to Inhibit Colon Cancer Growth

2013 ◽  
Vol 12 (5) ◽  
pp. 598-609 ◽  
Author(s):  
Sivapriya Ponnurangam ◽  
David Standing ◽  
Parthasarathy Rangarajan ◽  
Dharmalingam Subramaniam
Keyword(s):  
Colon Cancer ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Cancer Growth ◽  
Mtor Signaling Pathway

scholarly journals Ginsenoside Rg3 Suppresses Proliferation and Induces Apoptosis in Human Osteosarcoma

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yi Li ◽  
Jinying Lu ◽  
Furong Bai ◽  
Yanan Xiao ◽  
Yiran Guo ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Assay Method ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Ginsenoside Rg3 ◽  
Mtor Signaling Pathway ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

Osteosarcoma is the most common primary malignancy of bone in children and the elderly. Recently, more and more researches have demonstrated that Ginsenoside Rg3 (Rg3) is involved in chemotherapy resistance in many cancer, making it a promising Chinese herbal monomer for oncotherapy. In this study, we investigated the efficacy of Rg3 in human osteosarcoma cell lines (MG-63, U-2OS, and SaOS-2). Cell proliferation was measured by CCK8 assay. The migration of cells was examined using the scratch assay method. Quantification of apoptosis was assessed further by flow cytometry. In addition, the expression of apoptosis-related genes (caspase9, caspase3, Bcl2, and Bax) were investigated using RT-PCR. We further investigated the protein level expression of Bcl 2, cleaved-caspase3, and PI3K/AKT/mTOR signaling pathway factors by Western blot assay. Our results revealed that Rg3 inhibited the proliferation and migration of human osteosarcoma cells and induced apoptosis in a concentration- and time-dependent manner. Western blot results showed that Rg3 reduced the protein expression of Bcl2 and PI3K/AKT/mTORbut increased the levels of cleaved-caspase3. Therefore, we hypothesized Rg3 inhibits the proliferation of osteosarcoma cell line and induces their apoptosis by affecting apoptosis-related genes (Bcl2, caspase3) as well as the PI3K/AKT/mTOR signaling pathway. To conclude, Rg3 is a new therapeutic agent against osteosarcoma.

scholarly journals Inositol Hexaphosphate Inhibits Proliferation and Induces Apoptosis of Colon Cancer Cells by Suppressing the AKT/mTOR Signaling Pathway

Molecules ◽  
2017 ◽  
Vol 22 (10) ◽  
pp. 1657 ◽  
Author(s):  
Małgorzata Kapral ◽  
Joanna Wawszczyk ◽  
Katarzyna Jesse ◽  
Monika Paul-Samojedny ◽  
Dariusz Kuśmierz ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Colon Cancer Cells ◽  
Mtor Signaling Pathway ◽  
Inositol Hexaphosphate
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