Induction of Triple-negative Breast Cancer Cells to Immunogenic Cell Death and Increase Cross-Presentation by Streptomyces sanyensis

Articles

Abstract
Pharmacognosy Research,2021,13,3,165-172.
Published:June 2021
Type:Original Article
Authors:
Author(s) affiliations:

Xingguo Quan1, Ji-Young Lee2, Jin Hee Park1, Md. Masudul Haque1, Hee Yeon Kim3, Ilhwan Kim4, Anbok Lee3, Il-Whan Choi1, SaeGwang Park1,*

1Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, SOUTH KOREA.

2Department of Internal Medicine, College of Medicine, Inje University, Busan, SOUTH KOREA.

3Department of Surgery, College of Medicine, Inje University, Busan, SOUTH KOREA.

4Department of Internal Medicine, Division of Oncology Inje University College of Medicine, Haeundae Paik Hospital, Cancer Center, Busan, SOUTH KOREA.

Abstract:

Background: Biomass extract of Streptomyces sanyensis (BE-SS), which is a marine microorganism, has antitumor activity and has white-to-gray aerial mycelium and long chains of long spores in aerial mycelium. Objectives: The anti-cancer effect of BE-SS on triple-negative breast cancer (TNBC) was confirmed and cell death by BE-SS was confirmed to have immunogenicity and whether it could be used for immuno-cancer therapy. Materials and Methods: Human and mouse TNBC cells (MDA-MB-231, HS578T, 4T1-hemagglutinin (HA) and TUBO-P2J-HA cells) were treated with BE-SS at different concentrations for 72 hr and their cytotoxicity was detected using the sulforhodamine B-based (SRB) method. Flow cytometry was used to determine the type of cell death by Annexin V/7-AAD staining and to measure surface exposure to damage-related molecular pattern (DAMP) molecules including calreticulin (CRT), heat shock protein (HSP) 70/90. Carboxyfluorescein succinimidyl ester (CFSE) dilution assay was used to evaluate the immunogenicity of dead cells induced by BE-SS. Results: BE-SS reduced the viability of human (MDA-MB-231 and HS578T-cells) and mouse (4T1-HA and TUBO-P2J-HA cells) breast cancer cells. At 72 h, the IC50 of human and mouse breast cancer cells was 0.02-0.6 μg/ml and 0.005-0.37 μg/ml, respectively. BE-SStreated breast cancer cells were positively stained with Annexin V. Surface exposure to DAMP molecules increased in a dose-and time-dependent manner. CFSE dilution analysis showed that dendritic cells (DCs) fed with BE-SS treated breast cancer cells successfully stimulated tumor-specific T-cell proliferation without inhibiting DC function and T-cell proliferation. Conclusion: BE-SS can induce immunogenicity and apoptosis in breast cancer cells and may be a good adjuvant for TNBC immunotherapy.

PDF
Current View
Click here to download the PDF file.
Images

Graphical Abstract

Keywords