Medicinal Plant Research 2024, Vol.14, No.6, 358-370 http://hortherbpublisher.com/index.php/mpr 363 5 Antitumor Activity of Modified Cordyceps Polysaccharides 5.1 In vitro antitumor effects on cancer cell lines Chemically modified Cordyceps polysaccharides, such as selenization, acetylation, and nanoparticle encapsulation, have shown significant toxic effects on a variety of tumor cell lines in experiments. These cells include liver cancer (HepG2), lung cancer (A549), ovarian cancer (SKOV-3), colon cancer (HCT116), and tongue cancer (CAL-27) (Liu et al., 2017; Sun et al., 2018; Guan et al., 2020; Li et al., 2022). Many studies have shown that these modified polysaccharides can induce tumor cell death by activating the mitochondrial apoptosis pathway (intrinsic) and the death receptor pathway (exogenous). For example, common changes include increased levels of pro-apoptotic proteins such as Bax, caspase-3, caspase-9, and p53, while decreased levels of anti-apoptotic proteins such as Bcl-2 (Qi et al., 2020; Zheng et al., 2020; Zhang et al., 2023; Chen et al., 2024). These mechanisms do not occur in isolation, and sometimes occur together with cell cycle arrest, mainly concentrated in the G1 or S phase, which just limits the proliferation of tumor cells (Jing et al., 2014; Liu et al., 2019; Xu et al., 2021; Dai et al., 2024a; b). Of course, not all toxicity relies solely on apoptotic mechanisms. Some studies have also pointed out that modified Cordyceps polysaccharides can also induce ROS (reactive oxygen species) accumulation and enhance cytotoxicity by blocking autophagic flux, which is also one of the important means for them to exert anti-tumor effects (Li et al., 2022). More importantly, these compounds seem to have a certain degree of selectivity in killing tumor cells. In other words, they are effective against cancer cells, but relatively less toxic to normal cells (Liu et al., 2017; Chen et al., 2024). For example, selenium-enriched Cordyceps polysaccharides and acetylated nanoparticles show very low toxicity on normal endothelial cells or other animal cells, which is a positive signal for subsequent drug development (Liu et al., 2017; Qi et al., 2020). Some cordycepin derivatives also show good selectivity - they can effectively inhibit the growth of tumor cells, but have little effect on normal cells (Cui et al., 2024). 5.2 In vivo tumor suppression in animal models The anti-tumor effect of modified Cordyceps polysaccharides is not only determined by in vitro experiments, but also empirically supported by studies on animal models. Selenized polysaccharides and high molecular weight polysaccharides have performed well in a variety of tumor models. Whether it is xenografted SKOV-3 ovarian cancer, HepG2 liver cancer, Lewis lung cancer, or homografted S180 sarcoma and H22 liver cancer, there are obvious tumor inhibition responses (Liu et al., 2017; Bi et al., 2020; Shi et al., 2020; Liu et al., 2022; Li et al., 2022; Zhu et al., 2024; Sui et al., 2025). In most experiments, the tumor inhibition rate can be stabilized at more than 30% to 45%. Some are even close to the effectiveness of standard chemotherapy drugs, but with much fewer toxic side effects (Jing et al., 2014; Liu et al., 2017; Sui et al., 2025). Combination therapy is also a highlight. The combination of modified Cordyceps polysaccharides and conventional chemotherapy drugs such as cyclophosphamide and cisplatin not only enhances the anti-tumor effect, but also reduces the toxic burden of chemotherapy (Sui et al., 2025). In contrast, this combination treatment regimen appears to be milder but not ineffective in animal experiments. The histological results are also quite convincing. The number of apoptotic cells in the tumor tissues of the treated animals increased, while the proliferation activity weakened. The indexes of immune organs such as the spleen and thymus have rebounded, indicating that the immune status has improved (Tan et al., 2023; Dai et al., 2024a; b; Zhu et al., 2024). Further immunological tests found that the expression of pro-apoptotic proteins (such as TNF-α, IL-2, and IFN-γ) was enhanced, and the activity of macrophages and lymphocytes was also greatly improved, indicating that it does not fight alone, but fights tumors by activating the immune system (Bi et al., 2018; He et al., 2019; Dai et al., 2024a). Some studies have also mentioned that modified Cordyceps polysaccharides can also inhibit the formation of tumor angiogenesis and optimize the tumor microenvironment. Although this part of the mechanism is still under study, it has shown its multi-pathway potential (Lu et al., 2024).
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