Kentucky College of Osteopathic Medicine, University of Pikeville, Pikeville, KY, 41501, USA.
Department of Chemistry, University of Pikeville, Pikeville, KY, 41501, USA.
BMC Complement Altern Med. 2018 Feb 20;18(1):71. doi: 10.1186/s12906-018-2139-3.
Pancreatic cancer is one of the leading causes of cancer related death and its incidence has risen steadily. Although anticancer drugs have been developed based on the new molecular findings, the drugs have produced unsatisfactory results due to toxicity and resistance. Thus, a complementary therapeutic intervention is urgently needed for pancreatic cancer patients.
The aim of this study was to assess the potential therapeutic effect of Anacardic acid on pancreatic cancer in vitro and elucidate its underlying mechanisms. Human pancreatic cancer cells were treated with Anacardic acid and assessed for the cytotoxic effect using MTT and spheroid formation assays. Using the same methods, the synergy between Anacardic acid and 5-Fluorouracil or Gemcitabine was determined. To elucidate the underlying molecular mechanisms, Western blot analysis and immunocytochemistry were performed on cancer cells treated with Anacardic acid alone or in combination with 5-Fluorouracil or Gemcitabine. Chromatin Modifying Protein 1A (Chmp1A), Ataxia Telangiectasia Mutated (ATM), and p53 were the primary signaling molecules examined. In addition, Chmp1A was silenced with shRNA to examine the necessity of Chmp1A for the anticancer effect of Anacardic acid, 5-Fluorouracil, or Gemcitabine.
Anacardic acid induced an anticancer effect in pancreatic cancer cell lines in a dose dependent manner, and increased the cytotoxicity of 5-Fluorouracil or Gemcitabine in MTT cell viability assays. In spheroid formation assays, spheroids formed were smaller in size and in number upon Anacardic acid treatment compared to control. Mechanistically, Anacardic acid exerted its anticancer activity via the activation of Chmp1A, ATM, and p53. Interestingly, 5-Fluorouracil and Gemcitabine also induced an increase in Chmp1A protein level, suggesting that Chmp1A might mediate the cytotoxic action of chemotherapeutics. Silencing experiments indicate that Chmp1A is required for the action of Anacardic acid, but not for 5-Fluorouracil or Gemcitabine.
Our data suggests that Anacardic Acid might be a promising complementary supplement to slow the initiation or progression of pancreatic cancer.
胰腺癌是癌症相关死亡的主要原因之一，其发病率一直在稳步上升。尽管基于新的分子发现已经开发出抗癌药物，但由于毒性和耐药性，这些药物的效果并不理想。因此，迫切需要为胰腺癌患者提供补充治疗干预。
本研究旨在评估 Anacardic acid 对体外胰腺癌的潜在治疗效果，并阐明其潜在机制。用人胰腺癌细胞用 Anacardic acid 处理，并通过 MTT 和球体形成测定评估细胞毒性作用。使用相同的方法，确定 Anacardic acid 与 5-氟尿嘧啶或吉西他滨之间的协同作用。为了阐明潜在的分子机制，对单独用 Anacardic acid 或与 5-氟尿嘧啶或吉西他滨联合处理的癌细胞进行 Western blot 分析和免疫细胞化学分析。染色质修饰蛋白 1A (Chmp1A)、共济失调毛细血管扩张突变基因 (ATM) 和 p53 是主要检测的信号分子。此外，用 shRNA 沉默 Chmp1A，以研究 Chmp1A 对 Anacardic acid、5-氟尿嘧啶或吉西他滨的抗癌作用的必要性。
Anacardic acid 以剂量依赖性方式诱导胰腺癌细胞系中的抗癌作用，并增加 MTT 细胞活力测定中 5-氟尿嘧啶或吉西他滨的细胞毒性。在球体形成测定中，与对照组相比，用 Anacardic acid 处理后形成的球体体积更小且数量更少。在机制上，Anacardic acid 通过激活 Chmp1A、ATM 和 p53 发挥其抗癌活性。有趣的是，5-氟尿嘧啶和吉西他滨也诱导 Chmp1A 蛋白水平增加，表明 Chmp1A 可能介导化疗药物的细胞毒性作用。沉默实验表明，Chmp1A 是 Anacardic acid 作用所必需的，但不是 5-氟尿嘧啶或吉西他滨所必需的。
我们的数据表明，Anacardic Acid 可能是一种有前途的补充补充剂，可减缓胰腺癌的发生或进展。
