Astaxanthin Reduces Stemness Markers in BT20 and T47D Breast Cancer Stem Cells by Inhibiting Expression of Pontin and Mutant p53.

Yong Tae Ahn,Min Sung Kim,Won Gun An,Youn Sook Kim

doi:10.3390/md18110577

Abstract

Astaxanthin (AST) is a product made from marine organisms that has been used as an anti-cancer supplement. It reduces pontin expression and induces apoptosis in SKBR3, a breast cancer cell line. Using Western blotting and qRT-PCR analyses, this study revealed that in the T47D and BT20 breast cancer cell lines, AST inhibits expression of pontin and mutp53, as well as the Oct4 and Nanog cancer stem cell (CSC) stemness genes. In addition, we explored the mechanism by which AST eradicates breast cancer cells using pontin siRNAs. Pontin knockdown by pontin siRNA reduced proliferation, Oct4 and Nanog expression, colony and spheroid formation, and migration and invasion abilities in breast cancer cells. In addition, reductions in Oct4, Nanog, and mutp53 expression following rottlerin treatment confirmed the role of pontin in these cells. Therefore, pontin may play a central role in the regulation of CSC properties and in cell proliferation following AST treatment. Taken together, these findings demonstrate that AST can repress CSC stemness genes in breast cancer cells, which implies that AST therapy could be used to improve the efficacy of other anti-cancer therapies against breast cancer cells.

Highlights

Breast cancer, most frequently found in women with menopause, develops from breast tissue and is characterized by uncontrolled cell growth, with the ability to metastasize to other tissues [1].Risk factors for breast cancer include environmental mechanisms, genetic elements, and lifestyle components [2]
Mutp53 is restricted to poorly differentiated tumors, whereas the overexpression of wild-type p53 is restricted to less-differentiated areas of tumors [17]. These findings have demonstrated that mutp53 is associated with cancer stem cell (CSC) formation and poor prognosis [18]
Because spheroid formation ability is a characteristic of CSCs [27], we investigated spheroid formation ability in SKBR3, T47D, and BT20 breast cancer cell lines

Summary

Introduction

Most frequently found in women with menopause, develops from breast tissue and is characterized by uncontrolled cell growth, with the ability to metastasize to other tissues [1]. Risk factors for breast cancer include environmental mechanisms, genetic elements, and lifestyle components [2]. Natural therapeutic products that inhibit cancer cell growth without excessive toxicity are under investigation to identify candidate therapeutics [4]. AST has some effects against various types of cancer (e.g., oral, bladder, colon, blood, liver, lung, and breast). These effects are mediated by anti-proliferative, pro-apoptotic, antioxidant, anti-inflammatory, anti-invasion and migration, and anti-gap junctional intracellular communication mechanisms [6]. Potential molecular targets for AST in cancers include NF-kB, STAT3, P13K/AKT, MAPKs, PPAR, Nrf, and pontin [6,7]

Methods

Results

Conclusion