Ilimaquinone Induces Apoptosis and Autophagy in Human Oral Squamous Cell Carcinoma Cells.

Cheng-Wen Lin,Jing-Ru Weng,Wei-Yu Lin,Ming-Cheng Shih,Wei-Ting Huang,Jui-Hsin Su,Yu-Ting Huang,Chang-Fang Chiu,Li-Yuan Bai,Jing-Lan Hu

doi:10.3390/biomedicines8090296

Abstract

In this study, the anti-tumor activity of ilimaquinone (IQ), a sesquiterpene quinone isolated from marine sponge Halichondria sp., in oral squamous cell carcinoma (OSCC) cells, was investigated. IQ suppressed the viability of the OSCC cell lines SCC4 and SCC2095 with IC50 values of 7.5 and 8.5 μM, respectively. Flow cytometric analysis demonstrated that IQ induced caspase-dependent apoptosis in SCC4 cells and modulated the expression of several cell growth-related gene products, including Akt, p38, Mcl-1, and p53. Notably, p53 knockdown caused higher resistance to IQ’s anti-tumor activity. In addition, IQ increased reactive oxygen species generation, which was partially reversed by the addition of antioxidants. Furthermore, it triggered autophagy, as evidenced by acidic organelle formation and LC3B-II and Atg5 expression in SCC4 cells. Pretreatment with the autophagy inhibitor 3-methyladenine or chloroquine partially decreased IQ-induced apoptosis, suggesting that IQ induced protective autophagy. In summary, IQ has potential to be used in OSCC therapy.

Highlights

The incidence of oral squamous cell carcinoma (OSCC), which has a high mortality rate, has witnessed increases in developing counties, such as India [1,2]
Using MTT assays, the anti-viability effect of IQ was assessed in two OSCC cell lines: SCC4 and
This study reveals that, in OSCC cells (Figure 3A), IQ downregulated the expression of p-Akt, p-p38, and the metastasis prognostic marker HIF-1α [26]

Summary

Introduction

The incidence of oral squamous cell carcinoma (OSCC), which has a high mortality rate, has witnessed increases in developing counties, such as India [1,2]. The 5-year survival rate has remained at 50%, for the past decades [3], indicating the urgent need for new therapies. For over 34 years, natural products have provided ~40% of developed FDA-approved therapeutic agents [6]. The source of some of these therapeutic agents is the oceans, which contain a rich biodiversity of marine organisms [7]. Since 2010, eribulin mesylate, originally developed from halichondrin B, a macrocyclic polyether obtained from marine sponges, was approved as metastatic breast cancer therapy [8,9]. The ocean is a potential source of anti-tumor agents

Methods

Results

Conclusion