A newly synthesized oleanolic acid derivative inhibits the growth of osteosarcoma cells <b>in vitro and in vivo</b> by decreasing c‐MYC‐dependent glycolysis

Gao, Feng; Zuo, Qiang; Jiang, Tao; Song, Huanghe; Zhou, Jiahui

doi:10.1002/jcb.28202

Cited by 20 publications

(21 citation statements)

References 28 publications

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“…Xu et al (6) reported that OA inhibits osteosarcoma cell proliferation and viability and interrupts the balance between proapoptotic and antiapoptotic factors by inhibiting the Notch signaling pathway. Moreover, the derivative of OA, N-formyl morpholine substituent of CDDO (CDDO-NFM), leads to degradation of c-Myc and decreases glucose uptake, lactate generation and adenosine triphosphate production to block glycolysis (7). In the present study, compared with the Ctrl group, OA inhibited osteosarcoma cell proliferation and invasion, and enhanced cell apoptosis by inactivating the SOX9/Wnt1 signaling pathway.…”

Section: Discussionmentioning

confidence: 64%

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Oleanolic acid inhibits osteosarcoma cell proliferation and invasion by suppressing the SOX9/Wnt1 signaling pathway

Chen

Zhang

et al. 2021

Exp Ther Med

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Osteosarcoma is the most common primary bone malignancy in children and adolescents. Inhibition of SOX9/Wnt1-mediated signaling might suppress osteosarcoma metastasis, and oleanolic acid (OA) might decrease the activity of the SOX9/Wnt1 signaling pathway. The aim of the present study was to determine the role of OA in osteosarcoma cell proliferation and invasion. Osteosarcoma cell lines (KHOS and U2OS) and an osteoblastic cell line (hFOB1.19) were used for cell viability, proliferation and invasion analysis. The data suggested that OA significantly inhibited cell viability on days 3, 4 and 5 compared with the control (Ctrl) group in both U2OS and KHOS cells. Cell proliferation in the OA-treated group was significantly decreased compared with the Ctrl group in the osteosarcoma cell lines. Analysis of the cell cycle indicated that OA significantly reduced the percentage of U2OS and KHOS cells in the S phase compared with the Ctrl group. The wound healing assay results indicated that the OA group displayed significantly decreased cell re-colonization of the wound at 48 h compared with the Ctrl group. The Transwell chamber assay results also indicated that cell invasion was significantly inhibited by OA compared with the Ctrl group. Furthermore, OA significantly increased osteosarcoma cell apoptosis compared with the Ctrl group. Similarly, the protein expression levels of SOX9 and Wnt1 were significantly decreased in OA-treated U2OS and KHOS cells compared with Ctrl cells. OA-mediated downregulation of Wnt1 expression was reversed following SOX9 small interfering RNA transfection. Collectively, the results indicated that OA inhibited SOX9/Wnt1-associated osteosarcoma cell proliferation, migration and invasion.

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Section: Discussionmentioning

confidence: 64%

“…Oleanolic acid (OA), a naturally occurring triterpenoid, displays potential antitumor activity in several tumor cells, and has also has been reported to inhibit osteosarcoma cell proliferation and induce cell apoptosis (6)(7)(8). However, the mechanisms underlying OA during osteosarcoma are not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Oleanolic acid inhibits osteosarcoma cell proliferation and invasion by suppressing the SOX9/Wnt1 signaling pathway

Chen

Zhang

et al. 2021

Exp Ther Med

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“…Moreover, inhibition of c‐Myc activity exhibits an anti‐proliferative effect in many cancer cells . Molecular targeted therapies aimed at c‐Myc that interfere with c‐Myc synthesis, stability, and transcriptional activity have emerged as effective cancer treatments . It has been reported that c‐Myc could be regulated by CaMK II to facilitate cancer cell proliferation .…”

Section: Discussionmentioning

confidence: 99%

Ketamine inhibits aerobic glycolysis in colorectal cancer cells by blocking the NMDA receptor‐CaMK II‐c‐Myc pathway

Duan

Qing

2020

Clin Exp Pharma Physio

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Aerobic glycolysis plays a crucial role in cancer progression. Ketamine is often used for cancer pain relief in clinical settings. Moreover, ketamine inhibits proliferation and induces apoptosis in many cancer cell types. However, the anti‐tumour mechanism of ketamine is still poorly understood. In the present study, we survey whether and how ketamine inhibits aerobic glycolysis in colon cancer cells. Glycolysis of colon cancer cells was determined by detecting the extracellular acidification rate in HT29 and SW480 cells. Quantitative real‐time PCR was employed to determine mRNA expression. Calcium levels were detected with a Fluo‐3 AM fluorescence kit. Micro‐positron emission tomography/computed tomography (microPET/CT) imaging was employed to assess glycolysis in the tumours of the xenograft model. Ketamine treatment inhibited colon cancer cell viability and migration in HT29 and SW480 cells. Moreover, ketamine decreased aerobic glycolysis and decreased the expression of glycolysis‐related proteins in HT29 and SW480 cells. MicroPET/CT demonstrated that ketamine decreased 18F‐FDG uptake in the xenograft model. In addition, ketamine inhibited c‐Myc expression and CaMK II phosphorylation and decreased calcium levels. Further, dizocilpine (an NMDAR inhibitor), and KN93 (a CaMK II inhibitor), decreased CaMK II phosphorylation, c‐Myc expression, and cancer cell glycolysis; these results were similar to those with ketamine treatment. Furthermore, the anti‐tumour effect of ketamine was counteracted by rapastinel (an NMDAR activator). Ketamine inhibited aerobic glycolysis in colon cancer cells probably by blocking the NMDA receptor‐CaMK II‐c‐Myc pathway, thus attenuating colon cancer cell viability and migration.

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“…One component found in Chinese herbal medicine for hepatitis, oleanolic acid, has been modified chemically to create an oleanane triterpenoid,2-cyano-3-,12-dioxoolean-1,9-dien-28-oic acid (CDDO), a plant synthetized drug [8]. A master activator of antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), CDDO, has been found to impede the synthesis of inducible nitric oxide synthase and COX-2 in macrophages in mice [9] and has been found to affect cellular control of ROS/RNS levels which can set in motion the DNA damage associated with tumorigenesis [9].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of RTA 404 in Human Brain Malignant Glioma Cell Lines via Cell Cycle Arrest via p21/AKT Signaling

Tsai

Lieu

Wang

et al. 2021

BioMed Research International

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Background. Glioblastoma multiforme (GBM) is the most common malignant brain tumor in the world. Despite advances in surgical resection, radiotherapy, and chemotherapy, GBM continues to have a poor overall survival. CDDO (2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid), a synthetic triterpenoid, is an Nrf2 activator used to inhibit proliferation and induce differentiation and apoptosis in various cancer cells. One new trifluoroethylamide derivative of CDDO, RTA 404, has been found to have increased ability to cross the blood-brain barrier. However, it is not clear what effect it may have on tumorigenesis in GBM. Methods. This in vitro study evaluated the effects of RTA 404 on GBM cells. To do this, we treated GBM840 and U87 MG cell lines with RTA 404 and assessed apoptosis, cell cycle, cell locomotion, and senescence. DNA content and induction of apoptosis were analyzed by flow cytometry and protein expression by Western blot analysis. Results. RTA 404 significantly inhibited the proliferation of tumor cells at concentrations higher than 100 nM ( p < 0.05 ) and reduced their locomotion ability. In addition, treatment with RTA 404 led to an accumulation of RTA 404-treated G 2 / M phase cells and apoptosis. An analysis of the p21/AKT expression suggested that RTA 404 may not only help prevent brain cancer but it may also exert antitumor activities in established GBM cells. Conclusion. RTA404 can inhibit proliferation, cell locomotion, cell cycle progression, and induce apoptosis in GBM cells in vitro, possibly through its inhibition of N-cadherin and E-cadherin expression via its inhibition of the AKT pathway.

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A newly synthesized oleanolic acid derivative inhibits the growth of osteosarcoma cells in vitro and in vivo by decreasing c‐MYC‐dependent glycolysis

Cited by 20 publications

References 28 publications

Oleanolic acid inhibits osteosarcoma cell proliferation and invasion by suppressing the SOX9/Wnt1 signaling pathway

Oleanolic acid inhibits osteosarcoma cell proliferation and invasion by suppressing the SOX9/Wnt1 signaling pathway

Ketamine inhibits aerobic glycolysis in colorectal cancer cells by blocking the NMDA receptor‐CaMK II‐c‐Myc pathway

Therapeutic Potential of RTA 404 in Human Brain Malignant Glioma Cell Lines via Cell Cycle Arrest via p21/AKT Signaling

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