PMID- 37116152 OWN - NLM STAT- MEDLINE DCOM- 20230503 LR - 20230720 IS - 2476-762X (Electronic) IS - 1513-7368 (Print) IS - 1513-7368 (Linking) VI - 24 IP - 4 DP - 2023 Apr 1 TI - Anti-tumor Effects of IL-1beta Induced TRAIL-Expressing hUCMSCs on Embelin Treated Breast Cancer Cell Lines. PG - 1297-1305 LID - 90604 [pii] LID - 10.31557/APJCP.2023.24.4.1297 [doi] AB - BACKGROUND: Human umbilical cord mesenchymal stem cells (hUCMSCs) have high therapeutic value in cancer treatment. We have found that pre-activating hUCMSCs with IL-1beta promotes tumor necrosis factor-related apoptosis inducing ligand (TRAIL) expression and facilitates anti-tumor effect. Furthermore, embelin has been found to induce apoptosis of different cancer cell lines by upregulating the expression of TRAIL receptor 1 (DR4) and TRAIL receptor 2 (DR5). This study investigated whether IL-1beta induced TRAIL-expressing hUCMSCs, in combination with low-dose embelin, could further induce apoptosis in breast cancer cell lines. MATERIALS AND METHODS: MTT assay was used to examine the cytotoxicity of embelin in MDA-MB-231 and MCF-7. To detect the interested protein expression in cells, Western blot and cell immunofluorescence were used to double-confirm the observed results. Annexin V/PI apoptosis assay was detected by flow cytometry to analyze the apoptosis rate of embelin treated breast cancer cell lines and the effect of co-culturing with breast cancer cells and hUCMSCs. RESULTS: Using Western blot and immunofluorescence, we found that breast cancer cell lines treated with low-dose embelin (2.5-5 muM) increased the expression of apoptosis-related receptor DR4, DR5 and the cleaved caspase 8, 9 and 3. Moreover, TRAIL expression was enhanced in IL-1beta induced hUCMSCs. Combining these observations, we expected that coculturing IL-1beta induced hUCMSCs with low dose embelin treated MDA-MB-231 and MCF-7 cells might enhance the apoptosis of breast cancer cells. We confirmed via flow cytometry that coculture of IL-1beta induced TRAIL-expressing hUCMSCs and embelin treated MDA-MB-231 and MCF-7 cells enhances the apoptosis rate of these breast cancer cells. CONCLUSION: We found that embelin upregulated the expression of DR4 and DR5 to increase the TRAIL-mediated apoptosis in breast cancer cell lines. Low dose embelin treated breast cancer cell lines in combination with IL-1beta induced TRAIL-expressing hUCMSCs may become a potential anti-tumor therapy. FAU - Teng, Jui-Wen AU - Teng JW AD - Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, Taipei, Taiwan, ROC. FAU - Hung, Eric AU - Hung E AD - Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, Taipei, Taiwan, ROC. FAU - Wu, Jiann-Ming AU - Wu JM AD - General Surgery Division, Far Eastern Memorial Hospital, New Taipei City, Taiwan, ROC. FAU - Liang, Ya-Han AU - Liang YH AD - Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, Taipei, Taiwan, ROC. FAU - Chiu, Yun-Hsuan AU - Chiu YH AD - Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, Taipei, Taiwan, ROC. FAU - Tyan, Yeu-Sheng AU - Tyan YS AD - Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC. FAU - Wang, Hwai-Shi AU - Wang HS AUID- ORCID: 0000-0003-1818-0970 AD - Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, Taipei, Taiwan, ROC. LA - eng PT - Journal Article DEP - 20230401 PL - Thailand TA - Asian Pac J Cancer Prev JT - Asian Pacific journal of cancer prevention : APJCP JID - 101130625 RN - SHC6U8F5ER (embelin) RN - 0 (Ligands) RN - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand) RN - 0 (TNF-Related Apoptosis-Inducing Ligand) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Interleukin-1beta) SB - IM MH - Female MH - Humans MH - Apoptosis MH - *Breast Neoplasms/drug therapy MH - Cell Line, Tumor MH - Ligands MH - MCF-7 Cells MH - *Mesenchymal Stem Cells/metabolism MH - Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism MH - TNF-Related Apoptosis-Inducing Ligand/pharmacology MH - Tumor Necrosis Factor-alpha MH - Interleukin-1beta/pharmacology PMC - PMC10352746 OTO - NOTNLM OT - Human umbilical cord mesenchymal stem cells (hUCMSCs) OT - anti-tumor therapy OT - breast cancer cell OT - tumor necrosis factor-related apoptosis inducing ligand (TRAIL) COIS- The authors declare no conflicts of interest. EDAT- 2023/04/28 18:42 MHDA- 2023/05/01 06:42 PMCR- 2023/03/01 CRDT- 2023/04/28 16:07 PHST- 2022/12/06 00:00 [received] PHST- 2023/05/01 06:42 [medline] PHST- 2023/04/28 18:42 [pubmed] PHST- 2023/04/28 16:07 [entrez] PHST- 2023/03/01 00:00 [pmc-release] AID - 90604 [pii] AID - 10.31557/APJCP.2023.24.4.1297 [doi] PST - epublish SO - Asian Pac J Cancer Prev. 2023 Apr 1;24(4):1297-1305. doi: 10.31557/APJCP.2023.24.4.1297.