Lung cancer is the cancer with the highest mortality, and non-small cell lung cancer (NSCLC) accounts for more than 80%. Tumor cells often have high reactive oxygen species (ROS) and antioxidant capacity. Redox balance is very important for tumor. The decline of antioxidant capacity and excessive ROS will induce the death of tumor cells. Destroying the redox balance of tumor cells is a promising tumor treatment strategy. Xanthatin is an active sesquiterpene lactone isolated from Xanthium strumarium L. We observed that xanthatin induced the up regulation of mitochondrial ROS and mitochondrial damage. Meanwhile, our results showed that xanthatin could inhibit system x c − and reduce glutathione (GSH) synthesis. Antioxidant GSH and N-acetyl-L-cysteine (NAC) significantly reversed cell proliferation inhibition and apoptosis induced by xanthatin. β-Mercaptoethanol (β-ME) which can avoid inhibition of system x c − can also reverse the inhibition of cell proliferation induced by xanthatin, si-SLC7A11 was the opposite. Based on these results, we believe that the inhibition of xanthatin on the proliferation of NSCLC cells may be related to breaking the intracellular redox balance. Our data suggest that xanthatin is a promising antitumor candidate for the treatment of NSCLC.

Chemoresistance to cisplatin (DDP) therapy is a major obstacle that needs to be overcome in treating lung cancer patients. Xanthatin has been reported to exhibit an antitumor effect on various cancers, but the function of xanthatin in DDP‐resistance lung cancer remains unclear. The study aimed to explore the effect and mechanisms of xanthatin on proliferation, apoptosis, and migration in DDP‐resistance lung cancer cells. In the present study, xanthatin suppresses the expression of glucose transporter 1 (GLUT1), attenuates the pentose phosphate pathway (PPP), and causes ROS accumulation and apoptosis, thereby mitigating the antioxidative capacity in DDP‐resistance cells. Previous studies have shown that GLUT1 is associated with resistance to platinum drugs. We found that GLUT1 was significantly increased in the DDP‐resistant lung cancer cell line compared to the parental cell line, and xanthatin significantly downregulated GLUT1 expression in DDP‐resistant lung cancer cells. Notably, overexpression of GLUT1 significantly reduced the production of ROS and increased cellular NADPH/NADP+ and GSH/GSSG ratios. Thus, these results suggest that xanthatin induces DDP‐resistance lung cancer cells apoptosis through regulation of GLUT1‐mediated ROS accumulation. These findings might provide a possible strategy for the clinical treatment of DDP‐resistant lung cancer.

Disulfiram (DSF) has been used as a hangover drug for more than seven decades and was found to have potential in cancer treatment, especially mediated by copper. However, the uncoordinated...

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Background: Metastasis, a leading cause of cancer-related deaths, involves complex mechanisms. The premetastatic niche (PMN) is a crucial contributor to this process. Myeloid-derived suppressor cells (MDSCs) play an important role in PMN formation and promote tumor progression and metastasis. The Xiaoliu Pingyi recipe (XLPYR), a traditional Chinese medicine, is effective in preventing postoperative recurrence and metastasis in cancer patients. Objective: This study investigated the effects of XLPYR on MDSCs recruitment and on the expression of PMN markers and elucidated the mechanisms involved in the prevention of tumor metastasis. Methods: C57BL/6 mice were subcutaneously injected with Lewis cells and treated with cisplatin and XLPYR. Tumors were resected after 14 days after the establishment of a model of lung metastasis, and tumor volume and weight were measured. Lung metastases were observed 21 days after resection. MDSCs in the lung, spleen, and peripheral blood were detected by flow cytometry. Western blotting, qRT-PCR and ELISA were used to detect the expression of S100A8, S100A9, MMP9, LOX, and IL-6/STAT3 in premetastatic lung tissue. Results: XLPYR treatment inhibited tumor growth and prevented lung metastasis. Compared to mice without subcutaneous tumor cell transplantation, the model group had an increased proportion of MDSCs, higher expression of S100A8, S100A9, MMP9, and LOX in the premetastatic lung. XLPYR treatment reduced the proportion of MDSCs, S100A8, S100A9, MMP9, and LOX expression, and downregulated the IL-6/STAT3 pathway. Conclusions XLPYR may prevent MDSCs recruitment and reduce the expression of S100A8, MMP9, LOX, and IL6/STAT3 in premetastatic lung tissue, thus reducing lung metastases.