IJMMS_2024v14n6

International Journal of Molecular Medical Science, 2024, Vol.14, No.6, 324-341 http://medscipublisher.com/index.php/ijmms 332 Moreover, the modulation of other signaling pathways also affects the expression of apoptosis-related genes and proteins. For example, the inhibition of the PI3K/AKT pathway by GFP-A results in decreased expression of anti-apoptotic proteins and increased expression of pro-apoptotic proteins, enhancing apoptosis in HT-29 cells (Bie et al., 2020). Similarly, the activation of AMPK and inhibition of mTOR by PN50G leads to changes in the expression of proteins involved in cell cycle regulation and apoptosis, promoting cell death in A549 cells (Cui et al., 2016). Sanghuangporus polysaccharides induce tumor cell apoptosis through multiple mechanisms, involving the intrinsic and extrinsic pathways, as well as the modulation of other signaling pathways. The detection of apoptosis, study of signaling pathways, and analysis of gene and protein expression provide a comprehensive understanding of the molecular mechanisms underlying the antitumor effects of Sanghuangporus polysaccharides. These findings highlight the potential of Sanghuangporus polysaccharides as promising agents for cancer therapy. 5 Antioxidant Stress Effects of Sanghuangporus Polysaccharides and Their Antitumor Mechanisms 5.1 Relationship between oxidative stress and tumor development Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the body's ability to detoxify these reactive intermediates, plays a crucial role in the development and progression of tumors. Excessive ROS can damage cellular components, including DNA, proteins, and lipids, leading to mutations and genomic instability, which are hallmarks of cancer. The persistent oxidative environment promotes oncogenic signaling pathways, such as those involving NF-κB and HIF, which further drive tumorigenesis by enhancing cell proliferation, survival, and angiogenesis (Jiao et al., 2016). Moreover, oxidative stress can modulate the tumor microenvironment, making it more conducive to cancer progression. For instance, ROS can activate stromal cells and immune cells within the tumor microenvironment, leading to the secretion of pro-inflammatory cytokines and growth factors that support tumor growth and metastasis (Jiao et al., 2016). Therefore, targeting oxidative stress and its associated pathways presents a promising strategy for cancer prevention and therapy. 5.2 Analysis of antioxidant activity of Sanghuangporus polysaccharides Sanghuangporus polysaccharides have demonstrated significant antioxidant activities, which are pivotal in their antitumor effects. These polysaccharides can scavenge various free radicals, including DPPH, superoxide, and hydroxyl radicals, thereby reducing oxidative stress within the body (Shao et al., 2014; Wang et al., 2018). The antioxidant potential of Sanghuangporus polysaccharides is dose-dependent, with higher concentrations exhibiting greater free radical scavenging abilities (Wang et al., 2018). In addition to direct free radical scavenging, Sanghuangporus polysaccharides can enhance the body's endogenous antioxidant defense systems. For example, they have been shown to upregulate the expression of antioxidant enzymes such as superoxide dismutase (SOD) and catalase, which play critical roles in neutralizing ROS (Wang et al., 2018). This dual mechanism of action-direct scavenging of free radicals and boosting endogenous antioxidant defenses-makes Sanghuangporus polysaccharides potent agents against oxidative stress. 5.3 Mechanisms of tumor inhibition by Sanghuangporus polysaccharides through antioxidant stress Sanghuangporus polysaccharides inhibit tumor growth through multiple mechanisms, primarily by mitigating oxidative stress. By reducing ROS levels, these polysaccharides prevent the oxidative damage to DNA, proteins, and lipids that can lead to mutations and cancer progression. This reduction in oxidative stress also disrupts the oncogenic signaling pathways that are often activated by ROS, such as the NF-κB and HIF pathways, thereby inhibiting tumor cell proliferation and survival (Jiao et al., 2016). Furthermore, Sanghuangporus polysaccharides can induce apoptosis in tumor cells by modulating the expression of apoptosis-related genes. For instance, they have been shown to enhance the activation of p53-related genes, which are crucial for the induction of apoptosis in cancer cells (Wan et al., 2020). This activation leads to the downregulation of anti-apoptotic proteins like Bcl-2 and the upregulation of pro-apoptotic proteins like Bax,

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