β-elemonic acid inhibits the cell proliferation of human lung adenocarcinoma A549 cells: The role of MAPK, ROS activation and glutathione depletion

Wu,Tsu‑Tuan; Lu,Chien‑Lin; Lin,Hen‑I; Chen,Bing‑Fang; Jow,Guey‑Mei

doi:10.3892/or.2015.4368

β-elemonic acid inhibits the cell proliferation of human lung adenocarcinoma A549 cells: The role of MAPK, ROS activation and glutathione depletion

Authors:
- Tsu‑Tuan Wu
- Chien‑Lin Lu
- Hen‑I Lin
- Bing‑Fang Chen
- Guey‑Mei Jow
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Affiliations: Department of Respiratory Therapy, Fu Jen Catholic University, New Taipei City, Taiwan, R.O.C., Division of Nephrology, Department of Medicine, Shin‑Kong Wu Ho‑Su Memorial Hospital, Taipei, Taiwan, R.O.C., School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, R.O.C.
Published online on: October 30, 2015 https://doi.org/10.3892/or.2015.4368
Pages: 227-234

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Abstract

β-elemonic acid, a known triterpene, exhibits anti-inflammatory effects, yet research on the pharmacological effects of β-elemonic acid is rare. We investigated the anticancer effects and the related molecular mechanisms of β‑elemonic acid on human non‑small cell lung cancer (NSCLC) A549 cells. The effects of β‑elemonic acid on the growth of A549 cells were studied using a 3‑(4,5)‑2,5‑diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using Annexin V staining. The effect of β‑elemonic acid on the cell cycle of A549 cells was assessed using the propidium iodide method. The change in reactive oxygen species (ROS) was detected using a dichlorodihydrofluorescein diacetate (DCFH‑DA) assay with microscopic examination. The expression levels of Bcl‑2 family proteins, mitogen‑activated protein kinase (MAPK) family proteins and cyclooxygenase 2 (COX‑2) were detected using western blot analysis. Our data revealed that β‑elemonic acid strongly induced human A549 lung cancer cell death in a dose‑ and time‑dependent manner as determined by the MTT assay. β‑elemonic acid‑induced cell death was considered to be apoptotic when the phosphatidylserine exposure was observed using Annexin V staining. The death of human A549 lung cancer cells was caused by apoptosis induced by activation of ROS activity, increase in the sub‑G1 proportion, downregulation of Bcl‑2 expression, upregulation of Bax expression and inhibition of the MAPK signaling pathways. These results clearly demonstrated that β‑elemonic acid inhibits proliferation by inducing hypoploid cells and cell apoptosis. Moreover, the anticancer effects of β‑elemonic acid were related to the MAPK signaling pathway, ROS activation and glutathione depletion in human A549 lung cancer cells.

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