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Various reports show the beneficial effect of naringenin on the development of cancer. We hypothesized that naringenin suppresses cancer cells by activating intrinsic and extrinsic apoptosis pathways. This systematic review and meta-analysis was performed to reveal the effect of naringenin on cancer inhibition in vitro and in vivo by altering apoptotic factors. Literature search was carried out using electronic databases including PubMed, Web of Science, Scopus, Google Scholar, and Embase up to February 2021. The heterogeneity test of the included studies was performed using the PRISMA checklist protocol and I 2 statistic, respectively. Pooled standard mean difference and effect size (ES) with 95% confident interval (CI) were used to evaluate each relationship. A total of 32 articles were enrolled in our final analysis. Meta-analysis of the pooled findings for apoptosis, viability percentage, and apoptotic factors determined that treatment with naringenin affects viability and apoptosis in cancer cells in vitro and in vivo. Moreover, the results of in vitro experiments showed that naringenin increases the activity of caspase-3 (ES, 5.04; 95% CI, 2.61-7.47; I 2  = 99.9), caspase-9 (ES, 2.99; 95% CI, 2.47-3.51; I 2  = 93.7%), caspase-8 (ES, 2.86; 95% CI, 1.11-4.61; I 2  = 99.7%), and Bax expression (ES, 2.73; 95% CI, 1.91-3.55; I 2  = 99.4%) in cancer cells. It also increased the apoptotic rate and the activity of caspase-3 and caspase-9 in tumor-bearing animals. Overall, our findings highlight the potential therapeutic effects of naringenin in cancer inhibition through caspases cascade., Competing Interests: Conflict of Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

• Aryl hydrocarbons receptors (AhRs) are ligand-activated transcription factors. • Scientific data Analyze on the AhR signaling pathway and its interaction. • AhR signaling pathway seems to promote cell cycle progression. • Endogenous ligands is related to mitochondrial dysfunction. Mitochondria are ubiquitous membrane-bound organelles that not only play a key role in maintaining cellular energy homeostasis and metabolism but also in signaling and apoptosis. Aryl hydrocarbons receptors (AhRs) are ligand-activated transcription factors that recognize a wide variety of xenobiotics, including polyaromatic hydrocarbons and dioxins, and activate diverse detoxification pathways. These receptors are also activated by natural dietary compounds and endogenous metabolites. In addition, AhRs can modulate the expression of a diverse array of genes related to mitochondrial biogenesis and function. The aim of the present review is to analyze scientific data available on the AhR signaling pathway and its interaction with the intracellular signaling pathways involved in mitochondrial functions, especially those related to cell cycle progression and apoptosis. Various evidence have reported the crosstalk between the AhR signaling pathway and the nuclear factor κB (NF-κB), tyrosine kinase receptor signaling and mitogen-activated protein kinases (MAPKs). The AhR signaling pathway seems to promote cell cycle progression in the absence of exogenous ligands, whereas the presence of exogenous ligands induces cell cycle arrest. However, its effects on apoptosis are controversial since activation or overexpression of AhR has been observed to induce or inhibit apoptosis depending on the cell type. Regarding the mitochondria, although activation by endogenous ligands is related to mitochondrial dysfunction, the effects of endogenous ligands are not well understood but point towards antiapoptotic effects and inducers of mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]