Myrtucommulone-A treatment decreases pluripotency- and multipotency-associated marker expression in bladder cancer cell line HTB-9

Abstract

Cancer and stem cells exhibit similar features, including self-renewal, differentiation and immortality. The expression of stem-cell-related genes in cancer cells is demonstrated to be potentially correlated with cancer cell behaviour, affecting both drug response and tumor recurrence. There is an emerging body of evidence that subpopulations of tumors carry a distinct molecular sign and are selectively resistant to chemotherapy. Therefore, it is important to find novel therapeutic agents that could suppress the stem-like features of cancer cells while inhibiting their proliferation. Myrtucommulone-A (MC-A) is an active compound of a nonprenylated acylphloroglucinol isolated from the leaves of myrtle. Here we have investigated the potential of MC-A in inhibiting the expression of self-renewal regulatory factors and cancer stem cell markers in a bladder cancer cell line HTB-9. We used RT-PCR, immunocytochemistry, flow cytometry and western blotting to examine the expression of pluripotency- and multipotency-associated markers with or without treatment with MC-A. Treatment with MC-A not only decreased cancer cell viability and proliferation but also resulted in a decrease in the expression of pluripotency- and multipotency-associated markers such as NANOG, OCT-4, SOX-2, SSEA-4, TRA-1-60, CD90, CD73 and CD44. MC-A treatment was also observed to decrease the sphere-forming ability of HTB-9 cells. In summary, this study provides valuable information on the presence of stem-cell marker expression in HTB-9 cells and our results imply that MC-A could be utilized to target cancer cells with stem-like characteristics.

Cancer stem cells and epithelial–mesenchymal transition in urothelial carcinoma: Possible pathways and potential therapeutic approaches

“…found the treatment of MC‐A decreased cancer cell viability, proliferation and sphere‐forming ability in HTB‐9 cells, as well as the expression of common stem cell markers (e.g. NANOG, OCT4, SOX‐2, CD44) . Furthermore, they confirmed the functional inhibition of the EMT by MC‐A (thymoquinone was simultaneously analyzed) by testing the expression of EMT markers, and changes were found in the expression of proteins involved in the PI3K/AKT pathway; MC‐A and thymoquinone treatment inhibited the phosphorylation of those proteins in a context‐dependent manner .…”

“…Numerous studies have confirmed the expression of CD44 in UCSCs. At present, CD44 – especially CD44v6 – is the most commonly used CSC marker …”

“…For a long time, SOX2 was commonly regarded as a proper CSC marker. Over the past 10 years, the high expression of SOX2 has been used to recognize the presence of CSCs; this approach was applied in some studies on urothelial carcinoma …”

Stem-Like Signature Predicting Disease Progression in Early Stage Bladder Cancer. The Role of E2F3 and SOX4

“…SOX family of proteins are found in all metazoans, and high expression of SOX2 has been used to recognize the presence of CSCs. This approach has been applied in some studies of urothelial carcinoma [ 21 , 32 , 51 , 52 ].…”

Long Term Exposure to Myrtucommulone-A Changes CD105 Expression and Differentiation Potential of Mesenchymal Stem Cells

“…Myrtucommulone-A (MC-A) is an active compound isolated from the leaves of myrtle [12]. Previously we have shown that MC-A-treatment decreased multipotency-associated marker expression in cancer cells [13] and shortterm MC-A-treatment reduced the cytokine expression in hMSCs [14]. In the present study we sought to determine the long-term effects of MC-A on the stemness of hMSCs and analysed the differentiation potential of hMSCs upon extended MC-A-treatment.…”