Abstract
Safflower polysaccharide (SPS) is one of the active fractions extracted from safflower petals (Carthamus tinctorius L.) which has been reported to possess antitumor and immune control roles. However, its antitumor mechanisms by regulating the immune pathway remain barely understood. In this study, a mouse model was established by azoxymethane (AOM)/dextran sodium sulfate (DSS) to evaluate the antitumor effect of SPS on colorectal cancer (CRC). The results showed that 50 mg/kg SPS-1, an active fraction isolated from SPS, could significantly inhibit CRC induced by AOM/DSS and changed the polarization of macrophages to the M1 phenotype. Meanwhile, SPS-1 treatment significantly alleviated the characteristic AOM/DSS-induced pathological symptoms, in terms of decreasing the nucleoplasmic ratio, nuclear polarity extinction, and gland hyperplasia. However, the results in vitro showed that SPS-1 did not directly inhibit the growth of CRC cells but could upregulate the NF-κB signal and trigger M1 macrophage transformation. Thus, the condition medium (CM) of Mφ pretreated with SPS-1 was used against CRC cells. As expected, SPS-1–activated Raw 264.7 markedly exhibited antitumor effects by inhibiting cell proliferation and suppressing cell colony formation. In addition, SPS-1–activated Raw 264.7 could also induce CRC cell apoptosis by upregulating the levels of tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Further results suggested that SPS-1–induced transition of the macrophage phenotype could be suppressed by an NF-κB inhibitor, PDTC. Moreover, SPS-1–activated Raw 264.7 inhibiting CRC cell proliferation and inducing apoptosis were also rescued by PDTC. Taken together, all results suggested that SPS-1 could be a therapeutic option for the prevention and treatment of CRC.
Highlights
Colorectal cancer (CRC) is the third most common malignant tumor in the world, with morbidity and mortality second to gastric and liver cancer, respectively (Li et al, 2013; Mármol et al, 2017)
We found that Safflower polysaccharide (SPS)-1, an active fraction extracted from SPS, could significantly inhibit AOM/Dextran sulfate sodium (DSS)-induced colorectal cancer (CRC) in vivo
The repeated AOM challenges resulted in increasing levels of IL-6 and tumor necrosis factor-α (TNF-α) in serum and intestinal tissue, which contributes to AOM/DSS-induced CRC (Wang et al, 2019)
Summary
Colorectal cancer (CRC) is the third most common malignant tumor in the world, with morbidity and mortality second to gastric and liver cancer, respectively (Li et al, 2013; Mármol et al, 2017). In 2020, there were 1.93 million new cases of colon cancer, and 935,173 people died of colorectal cancer–related diseases (Siegel.et al, 2020). Most CRC cases are closely associated with environmental factors including chemicals and dietary causing genetic. To prevent colitis-related CRC, the discovery and development of drugs with small side effects and low tolerability are the current priorities. When evaluating the effects of drug candidates on CRC, it is crucial to select a suitable tumor model of CRC. According to short formation time, tumor stability, and similar characteristics to human CRC, the AOM/DSS model is the most suitable for studying the occurrence and development of CRC (Tanaka et al, 2003; Venkatachalam et al, 2020)
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