FIGURE 2.

An overview of mechanistic effects of natural metabolites in endocrine-independent HER-2 negative breast cancer (created with BioRender). (A) Diagrammatic representation of the mechanistic findings: cell death induction (Cheng et al., 2019; Guo and Pei, 2019; Nguyen et al., 2019; Zhang et al., 2019; Ding et al., 2020; Ho et al., 2020; Liu et al., 2020; Sánchez-Valdeolívar et al., 2020; Harikrishnan et al., 2021; Maungchanburi et al., 2021; Noh et al., 2021; Fouzat et al., 2022; Lin et al., 2022; Luo et al., 2022; Sancha et al., 2022; Sangpairoj et al., 2023), antiproliferative activity (Alsaraf et al., 2019; Zwartsen et al., 2019; Collard et al., 2020; Jaglanian and Tsiani, 2020; Kalebar et al., 2020; Lee et al., 2020; Mazzei et al., 2020; Yang et al., 2021; Lin et al., 2022; Youssef et al., 2022; Kombiyil and Sivasithamparam, 2023) antimetastatic activity (Hsu et al., 2020; Lee et al., 2020; Chen et al., 2022; Luo et al., 2022); antiangiogenic activity (Utage et al., 2018; Hsu et al., 2020; Zunica et al., 2021), disrupted cancer cell metabolism (Raman et al., 2018; Guerra et al., 2021; Yang et al., 2021; Chen et al., 2022; Ke et al., 2022), immunomodulation (Kim et al., 2018; Zhao et al., 2020; 2021; Deng et al., 2021; Chen et al., 2022; Fouzat et al., 2022; Lv et al., 2022). (B) Each mechanism of anticancer activity is described in details and recently studied organisms as a source of secondary metabolites are presented (full species names including authorities and family are presented in Table 1; Supplementary Table S1. Abbreviations: AKT, protein kinase B; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2; Bcl-w, B-cell lymphoma 2-like protein; Bcl-xL, B-cell lymphoma-extra-large; BC, Breast cancer; bFGF, basic fibroblast growth factor; CDK, cyclin-dependent kinase; EGFR, epidermal growth factor receptor; EGF-A, epidermal growth factor A; EMT, epithelial mesenchymal transition; ERK, extracellular signal-regulated kinase; HER-2, human epidermal growth factor receptor-2; IGF-I, insulin-like growth factor-I; IL, interleukin; MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; miRNA, microRNA; MMP, matrix metalloproteinase; NAD+, nicotinamide adenine dinucleotide (oxidized form); NADH, nicotinamide adenine dinucleotide (reduced form); NF-κB, nuclear factor-kappa B; PARP, poly (ADP-ribose) polymerase; PI3K, phosphatidylinositol-3-kinase; PD-L1, programmed death-ligand 1; p53, tumor protein 53; PTEN, phosphatase and tensin homolog; ROS, reactive oxygen species; STAT3, signal transducer and activator of transcription 3; TNF-α, tumor necrosis factor-alpha; VEGF, vascular endothelial growth factor; Wnt, wingless-related integration site.