Suppression of cyclooxygenase 2 increases chemosensitivity to sesamin through the Akt‑PI3K signaling pathway in lung cancer cells

Abstract

Safe, affordable and efficacious agents are urgently required for cancer prevention. Sesamin, a lipid-soluble lignan from sesame (Sesamum indicum) displays anticancer activities through an unknown mechanism. In the present study, the anticancer activity of sesamin via cyclooxygenase 2 (COX2) was investigated in lung cancer. Quantitative polymerase chain reaction was performed to determine the mRNA expression levels of COX2 in cells, while western blot analysis was used to determine its protein expression levels. Cell proliferation was evaluated by Cell Counting Kit-8 assay, while apoptosis and cell cycle analyses were conducted by flow cytometry. The results indicated that COX2 expression was upregulated in lung cancer cell lines compared with human normal lung epithelial cell line BEAS-2B and sesamin was demonstrated to decrease the levels of COX2, inhibit the proliferation of lung cancer cells and promote their apoptosis in a concentration-dependent manner. Furthermore, decreased COX2 expression potentiated sesamin-induced apoptosis and G1-phase arrest, which was correlated with the suppression of gene products associated with cell apoptosis (Bcl-2 and Bax) and the cell cycle (cyclin E1). In addition, cotreatment with the COX2 inhibitor CAY10404 and sesamin downregulated the expression of downstream molecules of COX2 [including interleukin (IL)1β, IL6 and tumor necrosis factor α] compared with CAY10404 or sesamin alone. Furthermore, cotreatment with sesamin and CAY10404 markedly reduced the levels of phosphorylated protein kinase B (pAkt) and phosoinositide 3 kinase (PI3K) in three lung cancer cell lines. PI3K expression was observed to be under the control of COX2, possibly forming a negative feedback loop. In addition, PI3K depletion induced apoptosis and G1-phase arrest in A549 cells. These results suggested that sesamin blocked the pAkt-PI3K signaling pathway by downregulating the expression of COX2, therefore resulting in cell cycle arrest and increased apoptosis in vitro. In conclusion, inhibition of COX2 increased the sensitivity of lung cancer cells to sesamin by modulating pAkt-PI3K signaling. These results may aid the development of more selective agents to overcome cancer.

Anti-Inflammatory and Anticancer Properties of Bioactive Compounds from Sesamum indicum L.—A Review

“…This action of sesamin showed that the lignan is capable of preventing DNA damage, hence, it becomes a potential anticancer agent. In line with this, it was also reported that the ability of sesamin to reduce COX-2 gene expressions in A549 cell line occurs through PI3K-Akt pathway [135] and inhibition of this pathway inactivates inflammatory response, which reduces restenosis [136].…”

Sesamin attenuates intestinal injury in sepsis via the HMGB1/TLR4/IL-33 signalling pathway

“…Sesamin is a lignin component isolated from sesame oil and is commonly considered a healthy food with antihypertensive, antiinflammatory, antiviral and antioxidative properties (Xu et al 2015). Additionally, the potential anticancer properties of sesamin in lung cancer, cervical cancer, and colon cancer have been reported in recent years (Dou et al 2018;Cavuturu et al 2019;Fang et al 2019). Previous evidence has shown that sesamin can inhibit lipopolysaccharide (LPS)-induced expression of Toll-like receptor (TLR) 4, which further results in repression of the inflammatory response (Qiang et al 2016).…”

Lipid peroxidation increases hydrogen peroxide permeability leading to cell death in cancer cell lines that lack mtDNA

“…However, it has been reported that HNE induces the expression of the COX2 gene, and that this expression is stabilized by the p38 mitogen‐activated protein kinase . In addition, COX2 has been reported to be involved in PI3K/Akt signaling . Recently, it was reported that administration of HNE decreased Akt phosphorylation and induced apoptosis in an osteosarcoma cell line .…”