Polymethoxylated flavone sudachitin is a safe anticancer adjuvant that targets glycolysis in cancer-associated fibroblasts.
Polymethoxylated flavone sudachitin is a safe anticancer adjuvant that targets glycolysis in cancer-associated fibroblasts.
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多甲氧基化黄酮sudachitin是一种安全的抗癌佐剂，靶向糖酵解在癌症相关的成纤维细胞。
DOI：
10.3892/ol.2022.13356
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发表时间：
2022-07
期刊：
影响因子：
2.9
通讯作者：
中科院分区：
文献类型：
--
作者：
苏达奇丁是在日本德岛县特有的柑橘类水果苏达奇的果皮中发现的多甲氧基化黄酮。已有研究表明，sudachitin具有抗炎和代谢调节活性。然而，据我们所知，还没有研究探讨sudachitin是否可以通过调节肿瘤微环境中的代谢功能来作为抗肿瘤治疗剂。在本研究中，细胞增殖和细胞毒性测定用于确定是否sudachitin抑制肝癌和胰腺癌，胆管癌和结直肠癌细胞的体外生长，并比较其对正常成纤维细胞和诱导的癌症相关成纤维细胞（CAFs）的毒性。采用乳酸测定法和逆转录-定量PCR法研究了sudachitin对CAFs糖酵解的影响。采用体外细胞增殖、创伤愈合和侵袭实验评价CAFs对恶性肿瘤细胞的作用。结果表明，苏丹草素对不同类型的肿瘤细胞具有不同的半数抑制浓度。用50 µM sudachitin处理48 h可抑制肿瘤和CAFs增殖，但对正常成纤维细胞无细胞毒性。该剂量还抑制CAF中的糖酵解，从而降低其促肿瘤活性。总的来说，本研究表明，sudachitin有希望作为一种安全和广泛使用的天然抗肿瘤佐剂。
Sudachitin is a polymethoxylated flavone found in the peel of Citrus sudachi, a unique specialty citrus fruit in Tokushima Prefecture, Japan. Previous reports have demonstrated that sudachitin has anti-inflammatory and metabolic regulatory activities. However, to the best of our knowledge, no studies have explored whether sudachitin can act as an antitumor therapeutic agent by regulating metabolic functions in the tumor microenvironment. In the present study, cell proliferation and cytotoxicity assays were used to determine whether sudachitin inhibited the in vitro growth of liver cancer and pancreatic carcinoma, cholangiocarcinoma and colorectal cancer cells and to compare its toxicity against normal fibroblasts and induced cancer-associated fibroblasts (CAFs). Using lactate assays and reverse transcription-quantitative PCR, the effects of sudachitin on glycolysis in CAFs were investigated. The effects of CAFs on malignant tumor cells were evaluated in vitro using cell proliferation, wound healing and invasion assays. As result, sudachitin inhibited various types of tumor cells with different half-maximal inhibitory concentrations. Treatment with 50 µM sudachitin for 48 h suppressed tumor and CAFs proliferation but was not cytotoxic against normal fibroblasts. This dose also inhibited glycolysis in CAFs and, thus, diminished their pro-tumorigenic activities. Overall, the present study revealed that sudachitin has promise as a safe and widely available natural antitumor adjuvant.
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