Anti-tumor Effects of IL-1β Induced TRAIL-Expressing hUCMSCs on Embelin Treated Breast Cancer Cell Lines.

Abstract

BACKGROUND:

Human umbilical cord mesenchymal stem cells (hUCMSCs) have high therapeutic value in cancer treatment. We have found that pre-activating hUCMSCs with IL-1β 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-1β 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 μM) increased the expression of apoptosis-related receptor DR4, DR5 and the cleaved caspase 8, 9 and 3. Moreover, TRAIL expression was enhanced in IL-1β induced hUCMSCs. Combining these observations, we expected that coculturing IL-1β 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-1β 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-1β induced TRAIL-expressing hUCMSCs may become a potential anti-tumor therapy.

• Authors: Jui-Wen Teng, Eric Hung, Jiann-Ming Wu, Ya-Han Liang, Yun-Hsuan Chiu, Yeu-Sheng Tyan, Hwai-Shi Wang
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 24 Issue 4 Pg. 1297-1305 (Apr 01 2023) ISSN: 2476-762X [Electronic] Thailand
• PMID: 37116152 (Publication Type: Journal Article)

Chemical References

• embelin
• Ligands
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• TNF-Related Apoptosis-Inducing Ligand
• Tumor Necrosis Factor-alpha
• Interleukin-1beta

Topics

• Female
• Humans
• Apoptosis
• Breast Neoplasms (drug therapy)
• Cell Line, Tumor
• Ligands
• MCF-7 Cells
• Mesenchymal Stem Cells (metabolism)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (metabolism)
• TNF-Related Apoptosis-Inducing Ligand (pharmacology)
• Tumor Necrosis Factor-alpha
• Interleukin-1beta (pharmacology)