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

Abstract

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.

Mechanisms underlying isoliquiritigenin‐induced apoptosis and cell cycle arrest via ROS‐mediated MAPK/STAT3/NF‐κB pathways in human hepatocellular carcinoma cells

“…Apoptosis is programmed cell death that is an important process in the pathogenesis of liver cancer (Goldar, Khaniani, Derakhshan, & Baradaran, ). Some studies have shown that the mitochondrial pathway can initiate and mediate apoptosis via regulation by Bcl‐2 family members, including Bcl‐xl, Bad, and Bax (Wang, Huang, et al, ; Wang, Wu, et al, ). It has been suggested that ISL induces apoptosis via inhibition of the STAT3 signaling pathway, and activating the mitochondrial pathway associated with cleavage of caspase‐3, ‐7, and ‐9, and increased the expression levels of Bax, decreasing the levels of Bcl‐2 and Bcl‐xl in human renal carcinoma Caki cells (Kim et al, ).…”

“…However, defects in the apoptotic process can cause uncontrolled cell proliferation and tumor formation (Mukherjee, Saviola, & Mackessy, ; Park et al, ). Phosphorylated mitogen‐activated protein kinases (MAPKs) regulate mitochondrial apoptotic pathways, as well as the expression of apoptosis‐related proteins, such as B‐cell lymphoma‐2 (Bcl‐2) family members, causing a cysteine aspartase (caspase) family cascade reaction and eventually inducing apoptosis (Wang, Huang, et al, ; Wang, Wu, et al, ). In addition, reactive oxygen species (ROS) accumulation, as well as signal transducer and activator of transcription 3 (STAT3) and nuclear factor‐kappa B (NF‐κB) pathways, play key roles in regulating apoptosis.…”

Anticancer effects of olive oil polyphenols and their combinations with anticancer drugs

“…The anticancer effects of Ole were also examined in vitro in human cervical cancer cells (84), PC cells (85), and neuroblastoma cells (86,87) and in vivo in the melanoma mouse model (38,88), with promising results. Two very recent studies demonstrated the beneficial effects of Ole in different types of lung cancers (89,90). The diversity of Ole's anticancer properties renders it a potential natural therapeutic in the future treatment of these malignant diseases.…”

By regulating miR-182-5p/<i>BCL10</i>/<i>CYCS</i>, sufentanil reduces the apoptosis of umbilical cord mesenchymal stem cells caused by ropivacaine

“…Cytochrome c (Cyt c), a heme-containing mitochondrial protein, has a critical function in both respiration and apoptosis. During apoptosis, cytochrome is released into the cytosol, where it subsequently participates in the process leading to caspase-9 and caspase-3 activation (35). The current results indicated that miR-182-5p expression was regulated in USMSCs by sufentanil or ropivacaine treatment, and that miR-182-5p improved cell survival and suppressed cell apoptosis by targeting BCL10 and CYCS expression.…”