Luo Dan, Luo Xu, Xie Jinghui, Ye Keying, Wang Xiangjin, Hu Xiyue, Liu Chenhao, Liu Yi
College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Front Pharmacol. 2025 May 16;16:1557088. doi: 10.3389/fphar.2025.1557088. eCollection 2025.
Cinnamaldehyde (CA), a naturally occurring aromatic aldehyde from cinnamon bark, has been investigated for its biological activity in laboratory settings. However, its α,β-unsaturated aldehyde structure designates it as a pan-assay interference compound (PAINS), which can produce non-specific effects through chemical reactivity-particularly in vitro-raising concerns about the validity and interpretation of its reported anti-tumor activity.
To systematically review and synthesize existing animal studies that examine the biological effects of CA on tumor growth, while critically evaluating the strength, limitations, and plausibility of the evidence, especially in light of CA's PAINS-related characteristics.
A systematic literature search was conducted across eight electronic databases to identify relevant animal studies assessing the effects of CA on tumor progression. Study quality was evaluated using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool. Quantitative synthesis was performed using Review Manager (RevMan) 5.3. studies were excluded due to concerns regarding non-specific activity and limited translatability.
Sixteen studies encompassing 19 independent experiments and 302 animals were included. Pooled results indicated that CA administration was associated with reductions tumor volume and tumor weight in animal models. However, no improvement in survival was observed, and CA-treated animals showed a modest decrease in body weight. Additionally, reduced expression of proliferating cell nuclear antigen (PCNA), hypoxia-inducible factor (HIF), vascular endothelial growth factor (VEGF), and microvessel density was reported. Despite these findings, the absence of controls for. Non-specific reactivity makes it difficult to distinguish true pharmacological effects from general cytotoxic or chemical stress responses.
While CA has demonstrated anti-tumor effects in animal models, these observations should be interpreted with caution. Its classification as a PAINS compound, coupled with a lack of mechanistic specificity, appropriate controls, and clinical validation, limits the reliability and translational relevance of the existing data. The observed outcomes are more likely reflective of non-specific chemical activity rather than targeted therapeutic action. Future research should prioritize rigorous mechanistic validation, use of non-reactive analogs, and comprehensive toxicity profiling before considering any clinical applicability.
肉桂醛（CA）是一种源自肉桂树皮的天然芳香醛，已在实验室环境中对其生物活性进行了研究。然而，其α,β - 不饱和醛结构使其被指定为泛测定干扰化合物（PAINS），它可通过化学反应产生非特异性效应——尤其是在体外——这引发了对其报道的抗肿瘤活性的有效性和解读的担忧。
系统回顾和综合现有动物研究，这些研究考察了CA对肿瘤生长的生物学效应，同时严格评估证据的强度、局限性和合理性，特别是鉴于CA与PAINS相关的特性。
在八个电子数据库中进行系统的文献检索，以识别评估CA对肿瘤进展影响的相关动物研究。使用实验室动物实验系统评价中心（SYRCLE）偏倚风险工具评估研究质量。使用Review Manager（RevMan）5.3进行定量综合分析。由于对非特异性活性和有限的可转化性的担忧，一些研究被排除。
纳入了16项研究，包括19个独立实验和302只动物。汇总结果表明，在动物模型中给予CA与肿瘤体积和肿瘤重量的减少有关。然而，未观察到生存率的改善，且接受CA治疗的动物体重略有下降。此外，有报道称增殖细胞核抗原（PCNA）、缺氧诱导因子（HIF）、血管内皮生长因子（VEGF）的表达降低以及微血管密度降低。尽管有这些发现，但缺乏对非特异性反应性的对照使得难以将真正的药理作用与一般细胞毒性或化学应激反应区分开来。
虽然CA在动物模型中已显示出抗肿瘤作用，但对这些观察结果应谨慎解读。其作为PAINS化合物的分类，再加上缺乏机制特异性、适当的对照和临床验证，限制了现有数据的可靠性和转化相关性。观察到的结果更可能反映的是非特异性化学活性而非靶向治疗作用。在考虑任何临床适用性之前，未来的研究应优先进行严格的机制验证、使用非反应性类似物以及全面的毒性分析。
