Journal
FRONTIERS IN PHARMACOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.779715
Keywords
thymopentin (TP5); colon cancer cells; oxaliplatin; AChRs; cancer stem cell (CSC)
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Funding
- National Natural Science Foundation of China [81603409, 31570832, 31971146]
- Natural Science Foundation of Jiangsu Province [BK20202002]
- Innovation and Entrepreneurship Talent Program of Jiangsu Province
- State Key Laboratory of Utilization of Woody Oil Resource [2019XK2002]
- Hunan Huxiang High-level Talent Program (2021)
- Xing Yao Leading Scholars of China Pharmaceutical University (2021)
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Thymopentin (TP5) is an immunomodulatory pentapeptide that inhibits the stemness of colon cancer cells and enhances the cytotoxicity of oxaliplatin (OXA). TP5 reduces stemness-related signals and alters Wnt/beta-catenin signaling by stimulating acetylcholine receptors (AchRs). This strategy provides promise for increasing sensitivity of colon cancer cells to chemotherapeutic agents.
Thymopentin (TP5) is an immunomodulatory pentapeptide that has been widely used in malignancy patients with immunodeficiency due to radiotherapy and chemotherapy. Here, we propose that TP5 directly inhibits the stemness of colon cancer cells HCT116 and therefore enhances the cytotoxicity of oxaliplatin (OXA) in HCT116 cells. In the absence of serum, TP5 was able to induce cancer stemness reduction in cultured HCT116 cells and significantly reduced stemness-related signals, such as the expression of surface molecular markers (CD133, CD44 and CD24) and stemness-related genes (ALDH1, SOX2, Oct-4 and Nanog), and resulted in altered Wnt/beta-catenin signaling. Acetylcholine receptors (AchRs) are implicated in this process. OXA is a common chemotherapeutic agent with therapeutic effects in various cancers. Although TP5 had no direct effect on the proliferation of HCT116, this pentapeptide significantly increased the sensitivity of HCT116 to OXA, where the effect of TP5 on the stemness of colon cancer cells through stimulation of AchRs may contribute to this process. Our results provide a promising strategy for increasing the sensitivity of colon cancer cells to chemotherapeutic agents by incorporating immunomodulatory peptides.
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