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Autophagy-modulating phytochemicals in cancer therapeutics: Current evidences and future perspectives
Seminars in Cancer Biology ( IF 14.5 ) Pub Date : 2020-05-22 , DOI: 10.1016/j.semcancer.2020.05.008
Srimanta Patra 1 , Soumya R Mishra 1 , Bishnu P Behera 1 , Kewal K Mahapatra 1 , Debasna P Panigrahi 1 , Chandra S Bhol 1 , Prakash P Praharaj 1 , Gautam Sethi 2 , Samir K Patra 3 , Sujit K Bhutia 1
Affiliation  

Autophagy is an intracellular catabolic self-cannibalism that eliminates dysfunctional cytoplasmic cargos by the fusion of cargo-containing autophagosomes with lysosomes to maintain cyto-homeostasis. Autophagy sustains a dynamic interlink between cytoprotective and cytostatic function during malignant transformation in a context-dependent manner. The antioxidant and immunomodulatory phyto-products govern autophagy and autophagy-associated signaling pathways to combat cellular incompetence during malignant transformation. Moreover, in a close cellular signaling circuit, autophagy regulates aberrant epigenetic modulation and inflammation, which limits tumor metastasis. Thus, manipulating autophagy for induction of cell death and associated regulatory phenomena will embark on a new strategy for tumor suppression with wide therapeutic implications. Despite the prodigious availability of lead pharmacophores in nature, the central autophagy regulating entities, their explicit target, as well as pre-clinical and clinical assessment remains a major question to be answered. In addition to this, the stage-specific regulation of autophagy and mode of action with natural products in regulating the key autophagic molecules, control of tumor-specific pathways in relation to modulation of autophagic network specify therapeutic target in caner. Moreover, the molecular pathway specificity and enhanced efficacy of the pre-existing chemotherapeutic agents in co-treatment with these phytochemicals hold high prevalence for target specific cancer therapeutics. Hence, the multi-specific role of phytochemicals in a cellular and tumor context dependent manner raises immense curiosity for investigating of novel therapeutic avenues. In this perspective, this review discusses about diverse implicit mechanisms deployed by the bioactive compounds in diagnosis and therapeutics approach during cancer progression with special insight into autophagic regulation.



中文翻译:

癌症治疗中的自噬调节植物化学物质:当前证据和未来前景

自噬是一种细胞内分解代谢的自我同类相食,通过将含有货物的自噬体与溶酶体融合来维持细胞稳态,从而消除功能失调的细胞质货物。自噬在恶性转化过程中以上下文依赖的方式维持细胞保护和细胞抑制功能之间的动态关联。抗氧化和免疫调节植物产品控制自噬和自噬相关的信号通路,以对抗恶性转化过程中的细胞无能。此外,在一个紧密的细胞信号回路中,自噬调节异常的表观遗传调节和炎症,从而限制了肿瘤转移。因此,操纵自噬以诱导细胞死亡和相关的调节现象将开启一种具有广泛治疗意义的肿瘤抑制新策略。尽管自然界中有大量的先导药效团,但中央自噬调节实体、它们的明确目标以及临床前和临床评估仍然是一个有待回答的主要问题。除此之外,自噬的阶段特异性调节和天然产物在调节关键自噬分子中的作用方式,与调节自噬网络相关的肿瘤特异性途径的控制在癌症中指定了治疗靶点。此外,预先存在的化学治疗剂与这些植物化学物质共同治疗的分子途径特异性和增强的功效对于靶向特异性癌症治疗具有很高的流行性。因此,植物化学物质在细胞和肿瘤环境依赖方式中的多特异性作用引起了对研究新治疗途径的巨大好奇心。从这个角度来看,这篇综述讨论了生物活性化合物在癌症进展过程中在诊断和治疗方法中部署的各种隐含机制,并对自噬调节有特别的了解。

更新日期:2020-05-22
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