Abstract

In this study, the anti-proliferative effect of ilimaquinone, a sesquiterpene derivative from the marine sponge, in breast cancer cells was investigated. Ilimaquinone inhibited the proliferation of MCF-7 and MDA-MB-231 breast cancer cells with IC50 values of 10.6 μM and 13.5 μM, respectively. Non-tumorigenic human breast epithelial cells were less sensitive to ilimaquinone than breast cancer cells. Flow cytometric and Western blot analysis showed that ilimaquinone induced S-phase arrest by modulating the expression of p-CDC-2 and p21. Ilimaquinone induces apoptosis, which is accompanied by multiple biological biomarkers, including the downregulation of Akt, ERK, and Bax, upregulation of p38, loss of mitochondrial membrane potential, increased reactive oxygen species generation, and induced autophagy. Collectively, these findings suggest that ilimaquinone causes cell cycle arrest as well as induces apoptosis and autophagy in breast cancer cells.

Highlights

  • Breast cancer has the highest incidence rate (73.2 per 100,000) among cancers in women

  • Compared with the breast cancer cells, ilimaquinone had a minimal effect on non-tumorigenic human breast epithelial cells H184BF5/M10 below 10 μM (Figure 1B)

  • Hood et al reported that peloruside A, a macrolide isolated from marine sponge, causes G2/M arrest by promoting microtubule polymerization in lung cancer cells [30]

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Summary

Introduction

Breast cancer has the highest incidence rate (73.2 per 100,000) among cancers in women. There are 324,000 deaths due to breast cancer, which is the most common cause of death in under developed countries in 2012 [3]. Chemotherapy, radiotherapy, hormone therapy, targeted therapy, and immunotherapy are the available treatments for breast cancer. The treatment of breast cancer ranges from 30,000 to 60,000 estimates by stage, which is an economic burden for patients [4]. The overall survival rate of breast cancer with chemotherapy is still below 34 months [5]. This highlights the urgent need for the development of new therapeutic strategies

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