datasheet1_Guaiazulene Triggers ROS-Induced Apoptosis and Protective Autophagy in Non-small Cell Lung Cancer.pdf

Non-small cell lung cancer (NSCLC) is one of the most frequent cancers worldwide, yet effective treatment remains a clinical challenge. Guaiazulene (GYZ), a cosmetic color additive, has previously been characterized as a potential antitumor agent due to observed anticancer effects. However, the efficacy of GYZ in the treatment of NSCLC and the involved molecular mechanisms remain largely unknown. Here, we indicated a role for GYZ in the suppression of NSCLC both in vitro and in vivo via triggering reactive oxygen species (ROS)-induced apoptosis. Concomitantly, GYZ induced complete autophagic flux in NSCLC cells via inhibiting the Akt/mTOR signaling pathway, which displayed cytoprotective effect against GYZ-induced growth suppression. Accompanied with autophagy inhibition obviously enhanced the effects of GYZ. Notably, GYZ acts synergistically with paclitaxel in the suppression of NSCLC in vitro. Together, our results for the first time reported that GYZ suppressed the proliferation of NSCLC and suggested a potential strategy for inhibiting NSCLC growth by combinational use of GYZ and autophagy inhibitors.

非小细胞肺癌（NSCLC）是全球最常见的癌症之一，然而有效的治疗手段仍面临临床挑战。茚三酮（Guaiazulene，GYZ），作为一种化妆品色素添加剂，先前因其所展现的抗癌效果而被表征为一种潜在的抗癌剂。然而，GYZ在治疗NSCLC中的疗效及其涉及的分子机制尚不清楚。本研究指出，GYZ通过触发活性氧（ROS）诱导的细胞凋亡，在体外和体内抑制NSCLC的生长。同时，GYZ通过抑制Akt/mTOR信号通路，诱导NSCLC细胞发生完全的自噬通量，表现出对GYZ诱导的生长抑制的细胞保护作用。伴随自噬抑制的明显增强，GYZ的效果得到显著提升。值得注意的是，GYZ在体外与紫杉醇协同作用，抑制NSCLC的生长。综合来看，我们的研究首次报道了GYZ抑制NSCLC增殖，并提出了通过GYZ与自噬抑制剂的联合使用来抑制NSCLC生长的潜在策略。（Non-small cell lung cancer (NSCLC), Guaiazulene (GYZ), reactive oxygen species (ROS), apoptosis, autophagic flux, Akt/mTOR signaling pathway, paclitaxel）