Oleuropein Induced Apoptosis in HeLa Cells via a Mitochondrial Apoptotic Cascade Associated With Activation of the c-Jun NH2-Terminal Kinase

Yao, Jie; Wu, Jibing; Yang, Xue; Yang, Jin‐Hui; Zhang, Yuxing; Du, Liang

doi:10.1254/jphs.14012fp

Cited by 44 publications

(45 citation statements)

References 66 publications

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“…4,9,[32][33][34][35] Therefore, the current study was performed to investigate the effects of oleuropein in H1299 cells. 4,9,[32][33][34][35] Therefore, the current study was performed to investigate the effects of oleuropein in H1299 cells.…”

Section: Discussionmentioning

confidence: 99%

“…38 These phenomena are in line with our experimental results, which showed increased Bax protein and decreased Bcl-2 protein ( Figure 2B). 4,9,39 In mammals, MAPK cascade is a highly conserved module that can be activated by a wide variety of different stimulation, while the JNK and p38 MAPK kinases are more responsive to stress stimulation including oxidative stress, UV irradiation, hypoxia, ischemia, and various cytokines. Moreover, we also observed the accumulation of sub-G1 cells, the increase of Hochest 33258-positive cells, and expression level of cleavage-PARP ( Figure 1D).…”

Section: Discussionmentioning

confidence: 99%

“…5 Oleuropein, which represents the predominant phenolic compounds, is an effective antioxidant compound, and possess various pharmacological properties, including anti-inflammatory, anticardiovascular disease, antimicrobial, antiviral, and antidiabetic effects. 4,8,9 Hence, this study was designed to investigate whether oleuropein exhibits the same antiproliferative and proapoptotic effects on NSCLC H1299 cells. 4,8,9 Hence, this study was designed to investigate whether oleuropein exhibits the same antiproliferative and proapoptotic effects on NSCLC H1299 cells.…”

Section: Introductionmentioning

confidence: 99%

“…11 It has been shown that p38 MAPK plays a critical role in the activation of the mitochondrial-mediated cell death pathway. 4,9 The current study was conducted to examine the effect of oleuropein in inducing apoptosis in human NSCLC H1299 cells, and the role of p38 MAPK involving in Bax expression, cytochrome c release, and the activation of caspases-3. 4,9 The current study was conducted to examine the effect of oleuropein in inducing apoptosis in human NSCLC H1299 cells, and the role of p38 MAPK involving in Bax expression, cytochrome c release, and the activation of caspases-3.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondria‐mediated apoptosis was induced by oleuropein in H1299 cells involving activation of p38 MAP kinase

Wang

Zhang

et al. 2018

J of Cellular Biochemistry

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Lung cancer is the main health threat in the world. Recently, oleuropein has been reported to have potent antioxidant and anticancer activities. However, the antitumor effects of oleuropein on H1299 cells are not well understood. Therefore, the purpose of this paper is tantamount to explore the effects of oleuropein on H1299 cells and its underlying mechanism that may be involved. Oleuropein treatment in H1299 cells resulted in cell cycle distribution at G2/M arrest and apoptosis in a dose‐dependent manner. Mitochondria‐mediated apoptosis was verified by the increase in Bax/Bcl‐2 ratio, release of cytochrome c, and activation of caspase‐3 on oleuropein‐induced H1299 cells. In addition, our data also demonstrated that the p38 mitogen‐activated protein kinase (MAPK) signaling pathway has a critical role in oleuropein‐induced apoptosis. Moreover, we used transcriptome analysis to identify differentially expressed genes (DEGs) in H1299 cells by oleuropein and SB203580 treatment. Many DEGs were annotated to metabolic pathways, cell cycle, pathways in cancer, MAPK signaling pathway by Kyoto Encyclopedia of Genes and Genomes and Gene ontology enrichment methods. Network and expression analysis found that DEGs, including RPS6A5, GADD45A, and MKP, play a key role in the p38 MAPK signaling pathway. In H1299 cells, oleuropein resulted in the expression of numerous genes related to cell signaling, metabolism pathway and directly associated with apoptosis. These results illustrated that oleuropein‐induced apoptosis via mitochondrial apoptotic cascade was activated by the p38 MAPK signaling pathway in H1299 cells. Thus, oleuropein as a natural compound and therapeutic drug has potential application value in the treatment of lung cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mitochondria‐mediated apoptosis was induced by oleuropein in H1299 cells involving activation of p38 MAP kinase

Wang

Zhang

et al. 2018

J of Cellular Biochemistry

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“…Work looking at the effects of oleuropein in MCF-7 has shown that it is able to induce apoptosis via up-regulating p53, and consequently the transcription of Bax/Bcl-2 apoptotic genes [62]. Other studies have also measured a change in p53 and Bax expression with oleuropein inhibition of cervical cancer cells [140] and p53 pathway up-regulation with oleuropein inhibition of colorectal cancer cells [61]. …”

Section: Olive Leaf Properties That Protect Against Development Anmentioning

confidence: 99%

Evidence to Support the Anti-Cancer Effect of Olive Leaf Extract and Future Directions

et al. 2016

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The traditional Mediterranean diet (MD) is associated with long life and lower prevalence of cardiovascular disease and cancers. The main components of this diet include high intake of fruit, vegetables, red wine, extra virgin olive oil (EVOO) and fish, low intake of dairy and red meat. Olive oil has gained support as a key effector of health benefits and there is evidence that this relates to the polyphenol content. Olive leaf extract (OLE) contains a higher quantity and variety of polyphenols than those found in EVOO. There are also important structural differences between polyphenols from olive leaf and those from olive fruit that may improve the capacity of OLE to enhance health outcomes. Olive polyphenols have been claimed to play an important protective role in cancer and other inflammation-related diseases. Both inflammatory and cancer cell models have shown that olive leaf polyphenols are anti-inflammatory and protect against DNA damage initiated by free radicals. The various bioactive properties of olive leaf polyphenols are a plausible explanation for the inhibition of progression and development of cancers. The pathways and signaling cascades manipulated include the NF-κB inflammatory response and the oxidative stress response, but the effects of these bioactive components may also result from their action as a phytoestrogen. Due to the similar structure of the olive polyphenols to oestrogens, these have been hypothesized to interact with oestrogen receptors, thereby reducing the prevalence and progression of hormone related cancers. Evidence for the protective effect of olive polyphenols for cancer in humans remains anecdotal and clinical trials are required to substantiate these claims idea. This review aims to amalgamate the current literature regarding bioavailability and mechanisms involved in the potential anti-cancer action of olive leaf polyphenols.

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The impact of oleuropein on miRNAs regulating cell death signaling pathway in human cervical cancer cells

Amini‐Farsani,

Hashemi Sheikhshabani,

Shaygan

et al. 2023

Biotech and App Biochem

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Cervical cancer is known as the second most pervasive malignancy in women across the globe. The role played by microRNAs (miRNAs) in the initiation, progression, and metastasis of this cancer has received specific attention. The use of natural compounds leading cancer cells toward apoptosis is a feasible strategy for cancer therapy. Oleuropein, an olive‐extracted phenolic substance, displays anticancer properties. Here, it was attempted to assess the role played by oleuropein in cell viability in cervical cancer and changes in the expression of some miRNAs associated with cervical cancer as well as some of their possible target genes selected using bioinformatics analysis. For this purpose, HeLa cell line was exposed to several oleuropein concentrations for 48 and 72 h. After that, 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide assay and flow cytometry were employed to assess cell viability and apoptosis, respectively. In addition, to conduct bioinformatics analysis, Cytoscape computer program was used based on STRING database. Furthermore, to examine the role played by oleuropein in the expression of miRNAs of interest as well as their potential target genes, real‐time PCR was employed. The findings indicated that oleuropein reduced cell viability through inducing apoptosis. As a result of treatment with oleuropein, miR‐34a, miR‐125b, and miR‐29a showed increased expression levels, whereas miR‐181b, miR‐221, and miR‐16 showed decreased expression levels. Furthermore, oleuropein reduced the expression of the anti‐apoptotic genes Bcl‐2 and Mcl1, whereas it elevated the expression of the pro‐apoptotic Bid, Fas, and TNFRSF10B genes and the p53 tumor suppressor. Our results indicate that the apoptosis induction is a mechanism of action of oleuropein in HeLa cells. Because of its effect on the reflation of the expression of genes and miRNAs effective in the pathogenesis of cervical cancer, oleuropein shows potential as an effective research tool for developing new natural drugs for treating cervical cancer.

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Oleuropein Induced Apoptosis in HeLa Cells via a Mitochondrial Apoptotic Cascade Associated With Activation of the c-Jun NH2-Terminal Kinase

Cited by 44 publications

References 66 publications

Mitochondria‐mediated apoptosis was induced by oleuropein in H1299 cells involving activation of p38 MAP kinase

Mitochondria‐mediated apoptosis was induced by oleuropein in H1299 cells involving activation of p38 MAP kinase

Evidence to Support the Anti-Cancer Effect of Olive Leaf Extract and Future Directions

The impact of oleuropein on miRNAs regulating cell death signaling pathway in human cervical cancer cells

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