Medicinal Plant Research 2024, Vol.14, No.6, 358-370 http://hortherbpublisher.com/index.php/mpr 365 Qi et al., 2020; Xu et al., 2021; Tan et al., 2023). Its apoptotic pathways include both intrinsic (mitochondrial-mediated) and extrinsic (death receptor-mediated) mechanisms, and are often accompanied by cell cycle arrest in the G1 or S phase, further inhibiting tumor cell proliferation (Liao et al., 2015; Xu et al., 2019; Zhang et al., 2023; Dai et al., 2024a). Cordyceps polysaccharides also interfere with tumor progression by inhibiting angiogenesis and metastasis. Its mechanisms include downregulating the expression of vascular endothelial growth factor (VEGF), inhibiting the activity of matrix metalloproteinases (MMPs), and regulating epithelial-mesenchymal transition (EMT)-related markers, thereby reducing tumor vascularization and metastatic potential (Qi et al., 2020; Liu et al., 2022; Gunter et al., 2025). The above effects are achieved by inhibiting key signaling pathways necessary for tumor cell migration and invasion (such as PI3K/Akt/mTOR, MAPK, and Hedgehog) (Liu et al., 2020; Lu et al., 2024; Sui et al., 2025). 6.3 Oxidative stress modulation and DNA damage response Cordyceps polysaccharides regulate the level of oxidative stress in tumor cells by increasing the generation of reactive oxygen species (ROS), thereby inducing mitochondrial dysfunction and caspase activation, leading to cell apoptosis (Chaicharoenaudomrung et al., 2018; Li et al., 2022; Zhang et al., 2023). Increased levels of ROS lead to oxidative damage, loss of mitochondrial membrane potential, and activation of intrinsic and extrinsic apoptotic pathways (Li et al., 2022; Zhang et al., 2023). It is worth noting that some cordyceps polysaccharides also have antioxidant properties and can protect normal cells from oxidative damage, demonstrating their dual role in redox regulation (Shi et al., 2020). In addition to inducing DNA damage, Cordyceps polysaccharides also regulate the expression of DNA repair genes and cell cycle regulatory factors. For example, they can upregulate the expression of p53 and other DNA damage response proteins, leading to cell cycle arrest in the S phase or G2/M phase, thereby inducing tumor cell apoptosis (Liao et al., 2015; Xu et al., 2019; Xu et al., 2021). This regulatory mechanism can weaken the DNA repair ability of tumor cells and enhance their sensitivity to anti-tumor treatment, thereby improving the therapeutic effect (Xu et al., 2019; Qi et al., 2020). 7 Case Studies of Chemically Modified Cordyceps Polysaccharides 7.1 Sulfated Cordyceps polysaccharides in anticancer applications Compared with unmodified native polysaccharides, sulfonated Cordyceps polysaccharides exhibit stronger antitumor activity. An animal experiment showed that low molecular weight α-glucan (LMW-CMP) derived from Cordyceps militaris inhibited tumor growth in the H22 tumor-bearing mouse model, with a tumor inhibition rate of 45.7% at a dose of 200 mg/kg (Dai et al., 2024b). Cordyceps cicadae polysaccharides also successfully inhibited the proliferation of HeLa cells by inducing cell cycle arrest and apoptosis, upregulating p53 expression, and activating caspase cascade reactions (Xu et al., 2021). There are few direct studies on the combined use of sulfonated Cordyceps polysaccharides and chemotherapeutic drugs, but relevant studies have shown that chemical modification of polysaccharides can enhance the efficacy of traditional chemotherapeutic drugs and reduce toxic side effects (Xie et al., 2020). For example, the anticancer activity of nanoparticles (DTX-AA-CSP nanoparticles) prepared by coupling Cordyceps polysaccharides with docetaxel on HepG2 and SW480 cells is superior to that of traditional docetaxel injection, showing potential synergistic therapeutic effects (Guan et al., 2020). In a mouse model of liver cancer, the combination of Cordyceps sinensis polysaccharide (CP1) and cyclophosphamide (CTX) can significantly improve the tumor inhibition rate and reduce toxic reactions such as bone marrow suppression (Sui et al., 2025). In the combined drug group, CP1 significantly enhanced the tumor inhibition effect of CTX, with the highest tumor inhibition rate reaching 77.63%, and can alleviate CTX-induced spleen atrophy and peripheral blood leukopenia, indicating that it has a significant immune protective effect (Figure 2).
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