Laboratory for Drug Design (LAPDESF), Drugs and Medicines Department, School of Pharmaceutical Sciences, University of São Paulo State, UNESP, Araraquara 14800-903, SP, Brazil.
Physiology and Pathology Department, School of Dentistry, University of São Paulo State, UNESP, Araraquara 14801-385, SP, Brazil.
Nutrients. 2024 Sep 10;16(18):3047. doi: 10.3390/nu16183047.
Colorectal cancer (CRC) is one of the top 10 most common cancers worldwide and caused approximately 10 million deaths in 2022. CRC mortality has increased by 10% since 2020 and 52.000 deaths will occur in 2024, highlighting the limitations of current treatments due to ineffectiveness, toxicity, or non-adherence. The widely used chemotherapeutic agent, 5-fluorouracil (5-FU), is associated with several adverse effects, including renal, cardiac, and hepatic toxicity; mucositis; and resistance. Taurine (TAU), an essential β-amino acid with potent antioxidant, antimutagenic, and anti-inflammatory properties, has demonstrated protective effects against tissue toxicity from chemotherapeutic agents like doxorubicin and cisplatin. Taurine deficiency is linked to aging and cancers such as breast and colon cancer. This study hypothesized that TAU may mitigate the adverse effects of 5-fluorouracil (5-FU). Carcinogenesis was chemically induced in rats using 1,2-dimethylhydrazine (DMH). Following five months of cancer progression, taurine (100 mg/kg) was administered orally for 8 days, and colon tissues were analyzed. The results showed 80% of adenocarcinoma (AC) in DMH-induced control animals. Notably, the efficacy of 5-FU showed 70% AC and TAU 50% while, in the 5-FU + TAU group, no adenocarcinoma was observed. No differences were observed in the inflammatory infiltrate or the expression of genes such as K-ras, p53, and Ki-67 among the cancer-induced groups whereas APC/β-catenin expression was increased in the 5FU + TAU-treated group. The mitotic index and dysplasia were increased in the induced 5-FU group and when associated with TAU, the levels returned to normal. These data suggest that 5-FU exhibits a synergic anticancer effect when combined with taurine.
结直肠癌（CRC）是全球最常见的癌症之一，2022 年导致约 1000 万人死亡。自 2020 年以来，CRC 死亡率增加了 10%，预计 2024 年将有 52000 人死亡，这突显了由于无效、毒性或不依从性等原因，当前治疗方法的局限性。广泛使用的化疗药物 5-氟尿嘧啶（5-FU）与多种不良反应相关，包括肾、心和肝毒性、黏膜炎和耐药性。牛磺酸（TAU）是一种必需的β-氨基酸，具有强大的抗氧化、抗突变和抗炎特性，已被证明对多柔比星和顺铂等化疗药物引起的组织毒性具有保护作用。牛磺酸缺乏与衰老和乳腺癌、结肠癌等癌症有关。本研究假设 TAU 可能减轻 5-氟尿嘧啶（5-FU）的不良反应。使用 1,2-二甲基肼（DMH）在大鼠中化学诱导致癌。在癌症进展五个月后，牛磺酸（100mg/kg）口服给药 8 天，并分析结肠组织。结果显示，DMH 诱导对照组动物中有 80%的腺癌（AC）。值得注意的是，5-FU 的疗效显示 70%的 AC 和 TAU 为 50%，而在 5-FU+TAU 组中未观察到腺癌。在诱导的癌症组中，炎症浸润或 K-ras、p53 和 Ki-67 等基因的表达没有差异，而 APC/β-连环蛋白的表达在 5-FU+TAU 治疗组中增加。有丝分裂指数和发育不良在诱导的 5-FU 组中增加，当与 TAU 联合使用时，水平恢复正常。这些数据表明，5-FU 与牛磺酸联合使用时具有协同抗癌作用。
