Antioxidant Peptide Derived fromSpirulina maximaSuppresses HIF1α-Induced Invasive Migration of HT1080 Fibrosarcoma Cells

Won Suk Kim,Sun Joo Park,Won Kyo Jung

doi:10.1155/2015/308602

Won Suk Kim, Sun Joo Park + Show 1 more

Open Access

https://doi.org/10.1155/2015/308602

Copy DOI

Abstract

Hypoxia causes the malignant progression of tumor cells; hence, it has been considered a central issue that must be addressed for effective cancer therapy. The initiation of tumor metastasis requires invasive cell migration. Here, we show that an antioxidant peptide derived fromSpirulina maximasuppresses hypoxia-induced invasive migration of HT1080 human fibrosarcoma cells. HT1080 cells treated with a hypoxia-inducing agent, CoCl2, exhibited an increase in invasive migration and intracellular reactive oxygen species (ROS), which is associated with an increase in the expression of hypoxia-induced factor 1α(HIF1α) accompanied by the activation of PI3K/Akt and ERK1/2. The inhibition of PI3K/Akt and ERK1/2 with specific inhibitors diminished the CoCl2-induced increase in HIF1αexpression and invasive cell migration. Moreover, CoCl2-induced HIF1αexpression was associated with an increase in the expression of molecules downstream ofβ-integrin, such as N-cadherin, vimentin, andβ-catenin. Therefore, theS. maximapeptide effectively attenuated the CoCl2-induced ROS generation and downregulated the HIF1αsignaling pathway involving PI3K/Akt, ERK1/2, andβ-integrin in cells. These results suggest that theS. maximaantioxidant peptide downregulates the HIF1αsignaling pathway necessary for hypoxia-induced invasive migration of HT1080 cells by attenuating intracellular ROS.S. maximapeptide may be an effective constituent in antitumor progression products.

Highlights

The rapid growth and proliferation of tumor cells result in a dramatic surge in oxygen demand
We first examined whether the peptide purified from S. maxima affects the invasive migration of highly metastatic HT1080 fibrosarcoma cells
The results demonstrated that treatment with the S. maxima peptide inhibited the invasive migration of HT1080 cells (Figure 1(a))

Summary

Introduction

The rapid growth and proliferation of tumor cells result in a dramatic surge in oxygen demand. Tumor hypoxia caused by inadequate oxygen supply is strongly associated with tumor propagation, malignant progression, and resistance to therapy [1, 2]. Accumulating evidence indicates that the effect of hypoxia on the malignant progression of tumor cells is mediated by a series of hypoxia-induced cellular changes that activate anaerobic metabolism, angiogenesis, and metastasis and enable tumor cells to survive or escape their oxygen-deficient environment [1, 3]. The transcription factor hypoxia-inducible factor 1 (HIF1), containing HIF1α and HIF1β subunits, has been known to be a key regulator in tumor cell adaptation to hypoxic environments. HIF1α regulates the expression of a number of genes affecting the metastatic progression of tumor cells [4,5,6]. HIF1α expression has been implicated in the increased invasive migration of tumor cells during the initiation of metastasis [2, 7]

Methods

Results

Conclusion