Background

The ability of cancer cells to divide without restriction and to escape programmed cell death is a feature of the proliferative state. Citrus flavanones are flavonoids with potential multiple anticancer actions, from antioxidant and chemopreventive, to anti-inflammatory, anti-angiogenic, cytostatic and cytotoxic in different cancer models.

Purpose

This review aims to summarize the current knowledge on the antiproliferative actions of the citrus flavanones hesperidin (HSD) and hesperetin (HST), with emphasis on cell cycle arrest and apoptosis.

Methods

Cochrane Library, Scopus, Pubmed and Web of Science collection databases were queried for publications reporting antiproliferative effects of HSD and HST in cancer models.

Results

HSD and HST have been proven to delay cell proliferation in several cancer models. Depending on the compound, dose and cell line studied, different effects have been reported. Cell cycle arrest associated with cytostatic effects has been reported in cells with increased levels of p53 and also cyclin-dependent kinase inhibitors, as well as decreased levels of specific cyclins and cyclin-dependent kinases. Moreover, apoptotic effects have been found to be associated with altered ratios of pro-/antiapoptotic proteins, caspase activation, c-Jun N-terminal kinase (JNK) pathway activation and caspase-independent pathways.

Conclusion

Available scientific literature data indicate complex effects, dependent on cell lines and exposure conditions, suggesting that HSD and HST doses need to be optimized according to the cellular and organismal context. The establishment of the main antiproliferative mechanisms is of utmost importance for a possible therapeutic benefit of citrus flavanones in the context of cancer.

中文翻译：

---

橙皮苷及其苷元橙皮苷的治疗潜力：癌症模型中的细胞周期调控和细胞凋亡诱导。

背景

癌细胞不受限制地分裂并逃脱程序性细胞死亡的能力是增殖状态的特征。柑橘类黄烷酮是类黄酮，具有潜在的多种抗癌作用，从抗氧化剂和化学预防剂到不同癌症模型中的抗炎药，抗血管生成药，细胞抑制药和细胞毒药。

目的

这篇综述旨在总结有关柑桔黄烷酮橙皮苷（HSD）和橙皮素（HST）的抗增殖作用的当前知识，重点是细胞周期停滞和凋亡。

方法

查询Cochrane图书馆，Scopus，Pubmed和Web of Science收集数据库，以获取报道HSD和HST在癌症模型中具有抗增殖作用的出版物。

结果

在几种癌症模型中，HSD和HST已被证明可延缓细胞增殖。根据所研究的化合物，剂量和细胞系，已报道了不同的​​作用。已经报道了在具有增加的p53水平以及细胞周期蛋白依赖性激酶抑制剂以及降低的特异性细胞周期蛋白和细胞周期蛋白依赖性激酶水平的细胞中，与细胞抑制作用相关的细胞周期停滞。而且，已经发现凋亡作用与改变的前/抗凋亡蛋白的比例，胱天蛋白酶激活，c-Jun N-末端激酶（JNK）途径激活和胱天蛋白酶非依赖性途径有关。

结论

现有的科学文献数据表明，取决于细胞系和暴露条件的复杂影响，表明HSD和HST剂量需要根据细胞和有机体的情况进行优化。建立主要的抗增殖机制对于柑桔类黄烷酮在癌症中可能的治疗益处至关重要。