Pancreatic cancer has a 5-year survival rate below 10% and the treatment options are limited. Signal transducer and activator of transcription (STAT3) is a constitutively expressed protein in human pancreatic cancers and is associated with their poor prognosis. Targeting of STAT3 signaling using novel therapeutic agents is a potential strategy for pancreatic cancer treatment. Diarylidenylpiperidone (DAP) compounds, such as H-4073 and HO-3867, have been shown to be STAT3 inhibitors in several human ovarian cancers. Particularly, HO-3867 is an N-hydroxypyrroline derivative of DAP that has targeted cytotoxicity toward cancer cells without affecting healthy cells. In the present study, we evaluated the anticancer efficacy of H-4073 and HO-3867 in a human pancreatic cell line (AsPC-1). We found that both the compounds exhibited potential cytotoxicity to AsPC-1 cells by inducing G2/M cell-cycle arrest, apoptosis, and cell death, by mitochondrial damage and inhibition of STAT3 phosphorylation. In summary, H-4073 and HO-3867 are cytotoxic to AsPC-1 cells and seem to act through similar mechanisms, including STAT3 inhibition, cell-cycle arrest, and apoptosis.

中文翻译：

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二芳基哌啶酮H-4073和HO-3867诱导人胰腺癌细胞G2 / M细胞周期阻滞，凋亡并抑制STAT3磷酸化。

胰腺癌的5年生存率低于10％，治疗选择有限。信号转导子和转录激活子（STAT3）是人类胰腺癌中组成型表达的蛋白，与预后不良有关。使用新型治疗剂靶向STAT3信号传导是胰腺癌治疗的潜在策略。二芳基哌啶酮（DAP）化合物，例如H-4073和HO-3867，已被证明是几种人类卵巢癌中的STAT3抑制剂。特别是，HO-3867是NDAP的-羟基吡咯啉衍生物，具有针对癌细胞的靶向细胞毒性而不影响健康细胞的能力。在本研究中，我们评估了H-4073和HO-3867在人胰腺细胞系（AsPC-1）中的抗癌功效。我们发现这两种化合物均通过诱导G2 / M细胞周期停滞，凋亡和细胞死亡，线粒体损伤和STAT3磷酸化抑制而对AsPC-1细胞表现出潜在的细胞毒性。总之，H-4073和HO-3867对AsPC-1细胞具有细胞毒性，并且似乎通过类似的机制起作用，包括STAT3抑制，细胞周期停滞和凋亡。