Resistance to apoptosis stands as a roadblock to the successful pharmacological execution of anticancer drug effect. A comprehensive insight into apoptotic signaling pathways and an understanding of the mechanisms of apoptosis resistance are crucial to unveil new drug targets. At this juncture, researchers are heading towards natural sources in particular, mushroom as their potential drugs leads to being the reliable source of potent bioactive compounds. Given the continuous increase in cancer cases, the potent anticancer efficacy of mushrooms has inevitably become a fascinating object to researchers due to their higher safety margin and multitarget. This review aimed to collect and summarize all the available scientific data on mushrooms from their extracts to bioactive molecules in order to suggest their anticancer attributes via a mitochondrion -mediated intrinsic signaling mechanism. Compiled data revealed that bioactive components of mushrooms including polysaccharides, sterols and terpenoids as well as extracts prepared using 15 different solvents from 53 species could be effective in the supportive treatment of 20 various cancers. The underlying therapeutic mechanisms of the studied mushrooms are explored in this review through diverse and complementary investigations: in vitro assays, pre-clinical studies and clinical randomized controlled trials. The processes mainly involved were ROS production, mitochondrial membrane dysfunction, and action of caspase 3, caspase 9, XIAP, cIAP, p53, Bax, and Bcl-2. In summary, the study provides facts pertaining to the potential beneficial effect of mushroom extracts and their active compounds against various types of cancer and is shedding light on the underlying targeted signaling pathways.

It has been recognized that miR-181a expression is dysregulated and intimately associated with clinical prognosis in a variety of human cancers. However, the direct role of miR-181a in tumor progression has been elusive. Moreover, mounting evidence has demonstrated that cellular apoptosis, a physiological process of programmed cell death, is disrupted in various categories of human malignancies. Multiple apoptosisrelated genes have been proven to act as the target genes of miR-181a. In this study, we hypothesize that miR-181a probably plays a potential role in modulating the procession and apoptosis of cancer cells. We performed a literature review and elucidated how miR-181a modulated cellular apoptosis, especially the malignant neoplasm cells. We also unraveled the potential role of miR-181a in the diagnosis, treatment and clinical prognosis of multiple human malignancies - miR-181a plays a pivotal role in the development, treatment and prognosis of patients suffering from malignant tumors. It also participates in the development of cancer partially by modulating cellular apoptosis.

Although Bcl-2 family proteins were originally identified as key regulators of apoptosis, an impressive body of evidence has shown that pro-survival members of the Bcl-2 family, including Bcl-2, Bcl-XL, and Bcl-w, can also promote cell migration, invasion, and cancer metastasis. Interestingly, cell invasion was recently found to be suppressed by multidomain pro-apoptotic members of the Bcl-2 family, such as Bax and Bak. While the mechanisms underlying these new functions of Bcl-2 proteins are just beginning to be studied, reactive oxygen species (ROS) have emerged as inducers of cell invasion and the production of ROS from mitochondrial respiration is known to be promoted and suppressed by the pro-survival and multidomain pro-apoptotic Bcl-2 family members, respectively. Here, I review the evidence supporting the ability of Bcl-2 proteins to regulate cancer cell invasion and metastasis, and discuss our current understanding of their underlying mechanisms, with a particular focus on mitochondrial respiration and ROS, which could have implications for the development of strategies to overcome tumor progression.