ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Lentinan inhibits colorectal cancer stemness by binding CD133 and suppressing the CD133/p85/p-AKT signaling axis
Provisionally accepted
- 1Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 2Huazhong University of Science and Technology Tongji Medical College, Wuhan, China
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Colorectal cancer (CRC) ranks third in the global cancer incidence rate worldwide. Cancer stem cells (CSCs) are key drivers of CRC recurrence, metastasis, and therapy resistance, while therapies against them remain limited. Lentinan is widely recognized for its strong immune-enhancing and broad-spectrum directly antitumor activities, however, whether it has potential for cancer stemness remains unknown. Our study aimed to assess the impact of lentinan on CRC stemness and its underlying mechanisms. Our results demonstrated that lentinan observably suppressed the proliferation of CRC cell lines HCT116 and SW620. Furthermore, tumor sphere formation and limiting dilution assays revealed that lentinan inhibited the stemness properties of CRC. Using cell sorting alongside cluster of differentiation 133 (CD133) knockdown and overexpression experiments, we confirmed that CD133 is a critical target through which lentinan exerts its anti-cancer effects. To elucidate the molecular mechanism, we performed localized surface plasmon resonance (LSPR), cellular thermal shift assay (CETSA), and molecular docking simulations. These experiments indicated that lentinan directly binds to the stemness marker protein CD133. Additionally, Western blot analysis showed that lentinan suppresses stemness by inhibiting the CD133/ phosphatidylinositol 3-kinase 85 kDa regulatory subunit (p85)/ phosphorylated AKT serine/threonine kinase (p-AKT) signaling axis in CRC. Our findings not only shed new light on the anti-tumor mechanism of lentinan, highlighting the scientific potential of natural polysaccharides in cancer treatment, but also offers new options for the clinical drug therapy of CRC.
Keywords: CD133, CRC, CSC - cancer stem cell, Shiitake β-glucan, Stemness
Received: 15 Oct 2025; Accepted: 26 Nov 2025.
Copyright: © 2025 Liu, Yang, Liu, He, Wang, Zhang, Wang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yu Zhang
Kaiping Wang
Jinglin Wang
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