Patra Srimanta, Mishra Soumya R, Behera Bishnu P, Mahapatra Kewal K, Panigrahi Debasna P, Bhol Chandra S, Praharaj Prakash P, Sethi Gautam, Patra Samir K, Bhutia Sujit K
Cancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela 769008, Odisha, India.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.
Semin Cancer Biol. 2022 May;80:205-217. doi: 10.1016/j.semcancer.2020.05.008. Epub 2020 May 22.
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.
自噬是一种细胞内分解代谢的自我吞噬过程，通过含货物的自噬体与溶酶体融合来清除功能失调的细胞质货物，以维持细胞内稳态。在恶性转化过程中，自噬以上下文依赖的方式维持细胞保护功能和细胞静止功能之间的动态联系。抗氧化和免疫调节植物产物控制自噬及自噬相关信号通路，以对抗恶性转化过程中的细胞功能障碍。此外，在紧密的细胞信号回路中，自噬调节异常的表观遗传调控和炎症，从而限制肿瘤转移。因此，操纵自噬以诱导细胞死亡及相关调节现象将开创一种具有广泛治疗意义的肿瘤抑制新策略。尽管自然界中先导药效团大量存在，但自噬核心调控实体、其明确靶点以及临床前和临床评估仍是有待回答的主要问题。除此之外，自噬的阶段特异性调控以及天然产物在调节关键自噬分子中的作用方式、与自噬网络调节相关的肿瘤特异性途径的控制，明确了癌症的治疗靶点。此外，现有化疗药物与这些植物化学物质联合治疗时的分子途径特异性和增强疗效，在靶向特异性癌症治疗中具有很高的普遍性。因此，植物化学物质在细胞和肿瘤背景依赖方式下的多特异性作用，引发了对研究新型治疗途径的极大兴趣。从这个角度来看，本综述讨论了生物活性化合物在癌症进展过程中的诊断和治疗方法中所采用的各种潜在机制，并特别深入探讨了自噬调节。
