Paper ID:9081

Effects of Conditioned Medium of Co-Culture IL2-Induced NK Cells and human Wharton’s Jelly Mesenchymal Stem Cells (hWJMSCs) on Apoptotic Genes Expression in a Breast Cancer Cells Line (MCF-7)

Wahyu Widowati*1, Diana Krisanti Jasaputra1, Philips Onggowidjaja1, Sutiman B. Sumitro2, M. Aris Widodo3, Ervi Afifah4, Dwi Davidson Rihibiha4, Rizal Rizal4, Harry Murti5 & Indra Bachtiar5,

1Faculty of Medicine, Maranatha Christian University, Bandung, West Java, Indonesia
2Faculty of Science, Brawijaya University, Malang, East Java, Indonesia
3Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia
4Biomolecular Biomedical Research Center,Aretha Medika Utama, Bandung, West Java, Indonesia
5Stem Cell and Cancer Institute, Jakarta, West Java, Indonesia

*Corresponding author: Wahyu Widowati, Faculty of Medicine, Maranatha Christian University, Prof. Drg. Suria Sumantri 65, Bandung, 40164, West Java, Indonesia

Email: wahyu_w60@yahoo.com

Received September 29, 2017, Revision May 9th, 2018, Accepted September 20th, 2018.

Abstract. Background: Breast cancer (BC) is the most known cancer among women and one of the major causes of cancer mortality prevalence in woman. The mortality of most patients with solid tumors is mainly due to metastatic spread to other organs. Metastasis in breast cancer (BC) occurs due to immunosurveillance deficiency including impairment of natural killer (NK) cell maturation. Therefore, the focus of recent cancer therapy is to promote developed-NK cells as drugs. Conditioned Medium (CM) from human Warton’s Jelly Mesenchymal Stem Cells     (hWJMSCs-CM) is known to possess anticancer activity. The CM of co-culture NK cells and hWJMSCs is expected to boost anticancer toward BC cells. Objective: To analyse the effect of CM of IL2-treated hWJMSCs towards secretion of effector molecules, BC cells’ apoptotic index and related genes expression, and cytotoxic granules in IL2-treated NK and hWJMSCs. Materials and Methods: Human recombinant IL-2 was used to induce NK cells (IL2-NK) and hWJMSCs (IL2-hWJMSCs). TNF-α, IFN-γ, perforin, granzyme were measured by ELISA. The inhibition of cell proliferation was measured by MTS. The BC cells apoptosis was measured by flow cytometry and apoptotic gene expression. Results: CM from IL2-treated hWJMSCs inhibit NK proliferation and BC cells. Co-culture of IL2-NK cells and hWJMSCs induced apoptosis, as well as increased expression of Bax and p53, and decreased Bcl-2 in BC cells.  Conclusion: CM of co-culture IL2-treated NK cells and hWJMSCs induce apoptosis in BC cells, as indicated by increased Bax and p53, and decreased Bcl-2 expression.

Keywords: breast cancer; conditioned medium; human Wharton’s jelly mesenchymal stem cells; interleukin-2; natural killer cells.

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