Anti-proliferation and anti-metastasis effect of barbaloin in non-small cell lung cancer via inactivating p38MAPK/Cdc25B/Hsp27 pathway

Abstract

Non-small cell lung carcinoma (NSCLC) is the most common lung cancer with high morbidity and mortality. The traditional treatment for NSCLC is particularly liable to relapse with many side-effects. Barbaloin is a natural compound with anticancer efficacy. The present study aimed to investigate the anticancer potential of barbaloin in NSCLC. The results displayed that barbaloin inhibited the viability of A549 cells by decreasing cell growth and the expression level of Ki-67 and proliferating cell nuclear antigen (PCNA), especially at high concentrations (50 and 100 µM). Besides, barbaloin increased the apoptosis rate of A549 cells and induced an accumulation of G2/M phase. Increased expression of apoptosis-related proteins (caspase-3, -8 and -9) and the changed levels of cell cycle checkpoint proteins (p27, p53 and cyclin A) further convinced of the anti-viability effect of barbaloin in A549 cells. On the other hand, barbaloin significantly suppressed the invasion and migration of A549 cells, and restrained the expression of tumor metastasis-related proteins. We further explored the activation of pro-survival or pro-metastasis signaling pathways, including AKT, nuclear factor kappa B (NF-κB), mitogen-actived protein kinase (MAPK) and β-catenin. The results revealed that barbaloin inactivated the p38MAPK/Cdc25B/Hsp27 pathway by inhibiting p38 nucleus translocation, while no significant influence was observed among other pathways. Finally, barbaloin restrained the growth and hepatic metastases of A549 cells in vivo. Taken together, our research indicated that barbaloin inhibited the proliferation and metastasis of NSCLC cells in vivo and in vitro. This may provide safer and more effective aspects for the treatment of NSCLC.

Apoptosis induction activity of polysaccharide from Lentinus edodes in H22-bearing mice through ROS-mediated mitochondrial pathway and inhibition of tubulin polymerization

“…Growing evidence has indicated that the generation of ROS could lead to cell apoptosis accompanied with triggering the activation of mitogen activated protein kinases (MAPKs), which include extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and p38MAPK ( 29 ). p38MAPK was regarded as one of the most important intracellular survival signal and frequently activated in diverse cancers, such as breast ( 30 ), liver ( 31 ), and lung ( 32 ) cancers, suggesting its role in cancer progression. Generally, suppression of p38MAPK pathway could result in cell cycle arrest, which was commonly regulated by cyclins (cyclin D1 and cyclin B1) and tumor suppressor protein p53.…”

“…A related study reported that treatment with barbaloin induced apoptosis and G2/M cell cycle arrest in A549 cells. Moreover, barbaloin suppressed the invasion and migration of A549 cells by the inactivation of p38MAPK pathway ( 32 ). Therefore, inhibition of p38MAPK pathway might be effective approaches for the treatment of cancers, including hepatocellular cancer.…”

Dioscin facilitates ROS-induced apoptosis via the p38-MAPK/HSP27-mediated pathways in lung squamous cell carcinoma

“…In colon cancer cells, dioscin activates the p38-MAPK signalling pathway to induce ROS-mediated apoptosis 17 . However, some controversial evidence has proven that inactivation of p38-MAPK inhibits tumorigenesis 33 , 34 . HSP27 is one of the downstream targets of p38-MAPK and high levels of HSP27 enhance the malignant behaviour of tumour cells, including over-proliferation, metastasis and less apoptosis 35 , 36 .…”

Xiaoai Jiedu Recipe Inhibits Proliferation and Metastasis of Non-Small Cell Lung Cancer Cells by Blocking the P38 Mitogen-Activated Protein Kinase (MAPK) Pathway

“…Previous research suggested that the p38 MAPK signaling pathway participates in the process of NSCLC [31]. Inactivation of the p38 MAPK signaling leads to anti-proliferation and anti-metastasis effects during NSCLC [13,32]. In addition, it has been reported that activation of p38 MAPK signaling promotes invasion and activates MMP-2 and MMP-9 expression [33].…”

“…The abnormal expression of apoptosis-related proteins, including Bcl-2, Bax, cleaved caspase-3, and cleaved caspase-9, were reported in a number of cancer studies [12]. It has been well documented that the p38 MAPK signaling pathway participates in the process of apoptosis in NSCLC cells, and the inactivation of p38 MAPK signaling can inhibit proliferation and induce apoptosis during NSCLC [13,14].…”