Oleic acid induces apoptosis and autophagy in the treatment of Tongue Squamous cell carcinomas

Lin Jiang,Zhonghua Liu,Wei Wang,Qianting He,Yisen Shao,Jingjing Sun,Yuan Wu,Anxun Wang,Zhiyuan Lu

doi:10.1038/s41598-017-11842-5

Abstract

Oleic acid (OA), a main ingredient of Brucea javanica oil (BJO), is widely known to have anticancer effects in many tumors. In this study, we investigated the anticancer effect of OA and its mechanism in tongue squamous cell carcinoma (TSCC). We found that OA effectively inhibited TSCC cell proliferation in a dose- and time-dependent manner. OA treatment in TSCC significantly induced cell cycle G0/G1 arrest, increased the proportion of apoptotic cells, decreased the expression of CyclinD1 and Bcl-2, and increased the expression of p53 and cleaved caspase-3. OA also obviously induced the formation of autolysosomes and decreased the expression of p62 and the ratio of LC3 I/LC3 II. The expression of p-Akt, p-mTOR, p-S6K, p-4E-BP1 and p-ERK1/2 was significantly decreased in TSCC cells after treatment with OA. Moreover, tumor growth was significantly inhibited after OA treatment in a xenograft mouse model. The above results indicate that OA has a potent anticancer effect in TSCC by inducing apoptosis and autophagy via blocking the Akt/mTOR pathway. Thus, OA is a potential TSCC drug that is worthy of further research and development.

Highlights

Traditional Chinese medicine (TCM) has been proven to have anti-tumor effects on many types of cancer
We performed a Cell Counting Kit-8 (CCK8) assay to examine the effect of Oleic acid (OA) on the proliferation of tongue squamous cell carcinoma (TSCC) cells (CAL27, UM1 cells)
The anti-proliferation effect of OA on TSCC cells was portrayed in a dose- and time-dependent manner

Summary

Introduction

Traditional Chinese medicine (TCM) has been proven to have anti-tumor effects on many types of cancer. Numerous studies have indicated that natural remedies or TCM have therapeutic effects on neoplastic diseases[1,2,3,4,5]. Both epidemiological and animal studies have reported a protective role of OA in several cancers, the beneficial effects of OA in TSCC remain unknown. To investigate the anticancer effect of OA on TSCC and the mechanism behind its anticancer effect, we first investigated the anticancer effect of OA on TSCC in vitro and in vivo, and the cell cycle, apoptosis, autophagy and the Akt/mTOR signaling pathway were further analyzed. OA induced cell cycle G0/G1 arrest, apoptosis, and autophagy by modulation of the Akt/mTOR pathway in the treatment of TSCC

Methods

Results

Conclusion