Oleanolic acid induces osteosarcoma cell apoptosis by inhibition of Notch signaling

Xu, Ying; Shu, Bing; Wang, Guangxi; Wang, Yongjun; Wang, Jinwu; Dong, Yufeng

doi:10.1002/mc.22810

Cited by 29 publications

(21 citation statements)

References 24 publications

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“…OA-induced cell death was ROS independent. OA has been reported to induce apoptosis in human hepatocellular carcinoma cells [21,22] , non-small cell lung cancer cell lines [23] , hypertrophic scar fibroblasts [24] and osteosarcoma cells [25] . In this investigation it was found that OA could decrease LO2 cell viability in a concentration-dependent manner.…”

mentioning

confidence: 99%

Oleanolic Acid Induces Apoptosis and Necrosis in Lo2 Cells

Xiao¹,

Yuanfu²,

Chen³

2020

pharmaceutical-sciences

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Xiao et al.: Oleanolic acid-induced cell death This study mainly focused on the evaluation of cytotoxicity of oleanolic acid on normal human hepatic cells. Normal human hepatic cells were exposed to different concentrations of oleanolic acid and the results demonstrated that oleanolic acid induced cell death in a concentration-and time-dependent manner in LO2 cells. Low concentration of oleanolic acid (40 μM) induced apoptosis. Cleavage of caspase 3/7/9 and decrease of mitochondrial membrane potential was detected in normal human hepatic cells. While high concentration of oleanolic acid (80 μM) caused necrosis without producing cleavage of caspase 3/7/9 or DNA fragmentation. Both flow cytometry and PI staining detected necrotic cells. In addition, both low and high concentrations of oleanolic acid had no effect on the generation of intracellular reactive oxygen species. Present data showed that oleanolic acid could induce apoptosis and necrosis in normal human hepatic cells. Oleanolic acid might be a potential hepatotoxin at high dosage.

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confidence: 99%

Oleanolic Acid Induces Apoptosis and Necrosis in Lo2 Cells

Xiao¹,

Yuanfu²,

Chen³

2020

pharmaceutical-sciences

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“…OA serves an antioncogenic role during malignant tumor development by inhibiting cancer cell proliferation, migration and invasion, and triggering cell death via apoptosis, autophagy or mitophagy (6,17,21). Multiple signaling pathways are associated with OA-mediated anticancer activities.…”

Section: Discussionmentioning

confidence: 99%

“…OA enhances osteosarcoma cell apoptosis. Previous studies have reported that OA increased cell apoptosis in other tumors (6,13); therefore, the effects of OA on osteosarcoma cell apoptosis were assessed. The TUNEL staining results suggested that OA significantly increased osteosarcoma cell apoptosis compared with the Ctrl group (Fig.…”

Section: Oa Inhibits Osteosarcoma Cell Proliferation and Invasionmentioning

confidence: 99%

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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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“…In a very recent study, (+)-oleanolic acid (6) was found to induce MG63 and Saos-2 human osteosarcoma cell apoptosis by targeting mitochondria in a Notch signaling-dependent manner [35]. By acting via a diverse range of cellular mechanisms, this endorses the potential of (+)-oleanolic acid for further development as an antitumor agent.…”

Section: Lupane-type Triterpenoidsmentioning

confidence: 93%

Natural Product Triterpenoids and Their Semi-Synthetic Derivatives with Potential Anticancer Activity

Ren

Kinghorn

2019

Planta Med

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Triterpenoids are distributed widely in higher plants and are of interest because of their structural diversity and broad range of bioactivities. In particular, there is a very large literature on the propensity of a variety of triterpenoids to act as potential anticancer agents. In the present review, the anticancer potential is summarized for naturally occurring triterpenoids and their semi-synthetic derivatives, including examples of lupane-, oleanane-, ursane-, and cucurbitane-type pentacyclic triterpenoids, along with dammarane-type tetracyclic triterpenes including ginsenosides and their sapogenins and dichapetalins, which have been characterized as antitumor leads from higher plants. Preliminary structure-activity relationships and reported mechanisms of the antineoplastic-related activity are included. Prior studies for triterpenoids of plant origin are supportive of additional work being conducted on the more detailed biological and mechanistic evaluation for the progression of this type of natural products as possible cancer chemotherapeutic agents.

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Oleanolic acid induces osteosarcoma cell apoptosis by inhibition of Notch signaling

Cited by 29 publications

References 24 publications

Oleanolic Acid Induces Apoptosis and Necrosis in Lo2 Cells

Oleanolic Acid Induces Apoptosis and Necrosis in Lo2 Cells

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

Natural Product Triterpenoids and Their Semi-Synthetic Derivatives with Potential Anticancer Activity

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