Decreased Inhibition of Proliferation and Induction of Apoptosis in Breast Cancer Cell Lines (T47D and MCF7) from Treatment with Conditioned Medium Derived from Hypoxia-Treated Wharton’s Jelly MSCs Compared with Normoxia-Treated MSCs

Wahyu Widowati; Harry Murti; Halida Widyastuti; Dian Ratih Laksmitawati; Rizal Rizal; Hanna Sari Widya Kusuma; Sutiman Bambang Sumitro; M. Aris Widodo; Indra Bachtiar

doi:10.18502/ijhoscr.v15i2.6038

Wahyu Widowati Faculty of Medicine, Maranatha Christian University, Jl. Prof. drg.. Suria Sumantri No.65, Bandung 40164, Indonesia
Harry Murti Stem Cell and Cancer Institute, Jl. A Yani No 2 Pulo Mas, Jakarta 13210, Indonesia
Halida Widyastuti Stem Cell and Cancer Institute, Jl. A Yani No 2 Pulo Mas, Jakarta 13210, Indonesia
Dian Ratih Laksmitawati Faculty of Pharmacy, Pancasila University, Jl. Raya Lenteng Agung No.56-80 Jakarta 12640, Indonesia
Rizal Rizal Biomolecular and Biomedical Research Center, Aretha Medika Utama,, Jl. Babakan Jeruk II No. 9, Bandung 40163, Indonesia
Hanna Sari Widya Kusuma Biomolecular and Biomedical Research Center, Aretha Medika Utama,, Jl. Babakan Jeruk II No. 9, Bandung 40163, Indonesia
Sutiman Bambang Sumitro Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Jl. Veteran, Ketawanggede Malang 65145, Indonesia
M. Aris Widodo Pharmacology Laboratories, Faculty of Medicine, Brawijaya University Jl. Veteran, Ketawanggede Malang 65145,, Indonesia
Indra Bachtiar Stem Cell and Cancer Institute, Jl. A Yani No 2 Pulo Mas, Jakarta 13210, Indonesia

DOI: https://doi.org/10.18502/ijhoscr.v15i2.6038

Keywords: Apoptosis; Breast cancer; Conditioned medium; Hypoxia; Wharton’s jelly-derived mesenchymal stem cells

Abstract

Background: Mesenchymal stem cells (MSCs) are an appealing source of adult stem cells for cell therapy due to the high rate of proliferation, self-renewal capability, and applicable therapy. Wharton’s jelly (WJ), the main component of the umbilical cord extracellular matrix, comprises multipotent stem cells with a high proliferation rate and self-renewal capability and has anti-cancer properties. MSCs have been reported to secrete a variety of cytokines that have a cytotoxic effect in various cancers. Oxygen tension affects MSCs proliferation, cytokines level but no in surface markers expression, MSCs’ differentiation. We explored the cytotoxic effect and inducing apoptosis of Wharton’s jelly derived mesenchymal stem cells (WJMSCs) secretions from normoxic WJMSCs (WJMSCs-norCM) (CM: conditioned medium) and hypoxic WJMSCs (WJMSCs-hypoCM) in breast cancer cell lines (T47D and MCF7).

Materials and Methods: Cytotoxic activity was determined using the MTS assay. RT-PCR was performed to measure the expression of apoptosis-inducing genes, specifically P53, BAX, and CASP9, and the antiapoptotic gene BCL-2.

Results: WJMSCs-norCM and WJMSCs-hypoCM were potent inhibitors of the proliferation in both cell lines. WJMSCs-norCM had more anticancer activity in T47D and MCF7. The IC50 value of WJMSCs-norCM on MCF7 was 42.34%, and on T47D was 42.36%. WJMSCs-norCM significantly induced the gene expression of apoptotic P53, BAX, and CASP9 and insignificantly decreased the antiapoptotic gene BCL-2 in both MCF7 and T47D cells. WJMSCs-CM has anticancer activity by inducing P53, BAX, and CASP9 apoptotic genes. Conclusion: WJMSCs-norCM has more anticancer activity than WJMSCs-hypoCM.