The Ethanol Extract of Marine Sponge Aaptos suberitoides Suppress Cell Viability, Cell Proliferation and Cell Migration in HER2-Positive Breast Cancer Cell Line.

Muhammad Hasan Bashari,Fadli Zaky Arsydinilhuda,Annisa Dewi Nugrahani,Ajeng Kartika,Tenny Putri,Ryzkianty Annis Nurdin,Edy Meiyanto,Fathul Huda,Yunisa Pamela,Eko Fuji Ariyanto,Nurul Qomarilla,Ikhwan Resmala Sudji,Hermin Aminah Usman,Beginer Subhan,Harold Atmaja,Maman Abdurahman,Re Septian Ilhamsyah

doi:10.31557/apjcp.2021.22.s1.25

Abstract

This study aimed to investigate the cytotoxicity, anti-proliferation and anti-migration effect of the ethanol extract of Aaptos suberitoides on trastuzumab-resistant HER2+ breast cancer cell line. Aaptos suberitoides was collected from Tinjil Island, Banten, Indonesia, and was processed with maceration and ethanol extraction. HCC-1954 cells were treated with the ethanol extract and then followed by 3- [4, 5-dimethylthiazol-2-yl] -2.5 diphenyl tetrazolium bromide (MTT) assay to assess cytotoxicity, clonogenic assay and three-dimensional (3D) spheroid assay to evaluate anti-proliferative effect in two-dimensional and 3D model, respectively, and wound healing assay to determine anti-cell migration effect. Four parametric regression was used to analyse the IC50. This study revealed that the ethanol extract of Aaptos suberitoides suppressed cell viability in correlation with cell death induction. The IC50 values of the ethanol extract of Aaptos suberitoides using MTT assay and clonogenic assay were 12.0 ppm and 4.36 ppm, respectively. The extract demonstrated an inhibition effect on spheroid growth. In low concentration, the extract of Aaptos suberitoides inhibited cell migration. Furthermore, MS analysis showed that the most abundant compounds in this extract has molecular weight m/z 229.81 [M+H]+. This study revealed that the ethanol extract of Aaptos suberitoides demonstrates cytotoxicity, anti-proliferation and anti-migration effect as well as inhibition effect on three-dimensional spheroid growth in trastuzumab-resistant HER2+ breast cancer cell line.<br />.

Highlights

Breast cancer (BC) is the most common cancer and the leading cause of cancer death among women across the world (Forouzanfar et al, 2016)
Pathogenesis of human epidermal growth factor 2 (HER2)+ BC comprises many molecular pathways that lead to cell survival, uncontrolled cell proliferation, and migration
Lower level of protein 21 (p21), a cyclin-dependent kinase inhibitor (CDKI), and Activator protein 1 (AP-1) in HER2+ BC was proposed to be responsible for cell’s survival and proliferation, while the high tendency for metastasis in HER2+ BC was associated with modulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (Dyshlovoy et al, 2014; Kumar et al, 2015)

Summary

Introduction

Breast cancer (BC) is the most common cancer and the leading cause of cancer death among women across the world (Forouzanfar et al, 2016). Aaptos suberitoides marine sponges are abounded in West Pacific Ocean especially in Indonesia, Singapore, and Vietnam (Halanych, 2004) They are sessile organisms having the ability to produce high secondary metabolites and to synthesize a variety of organic compounds such as polyketide, alkaloid, peptide, and terpene (Nurhayati et al, 2018). Recent data showed the close relevance of 3-dimensional (3D) spheroid cell culture methods in comparison with in vivo outcome (Friedrich et al, 2009; Vinci et al, 2012; Hsiao et al, 2012; Breslin et al, 2013; Thoma et al, 2014; Breslin and O’Driscoll, 2016) This method of cell culture has never been conducted in previous research with marine sponge Aaptos suberitoides. The effect of sponge in HER2+BC cell’s migration ability was evaluated using wound healing assay

Materials and Methods

Results

Discussion