Table 3.
Pre-clinical studies demonstrating high effectiveness of flavonoids as anti-inflammatory agents against tumor progression
| Flavonoid | Study details | Mechanisms | Effect | Reference |
|---|---|---|---|---|
| Biochanin A | Coculture method—lung cancer A427 cell lines cocultured with monocytic leukemic AML-193 cells | Inhibited TNF-α and IL-6; repressed invasion; altered EMT markers (reduced Snail and increased E-cadherin) | Represses pro-inflammatory responses, invasion, migration, and metastasis | [144] |
| Diosmetin | Glioma U251 cells | Inhibited TGF-β; increased E-cadherin | Inhibited migration and invasion | [143] |
| Hesperetin | Hepatic cancer HepG2 cells | Suppressed NF-κB activation; reduced TNF-α and IL-6; reduced ROS overproduction by the Nrf2 pathway | Reduced inflammatory cytokine secretion | [145] |
| EGCG | Pancreatic cancer Panc-1 and MIA PaCa-2 cells | Inhibited AKT, modulated EMT markers (increased E-cadherin and decreased N-cadherin), decreased mesenchymal markers (TCF8/ZEB1, β-catenin, and vimentin) | Suppressed invasion, migration, and metastasis | [146] |
| LFG-500 | TGF-β-induced model of EMT (breast cancer MCF-7 and lung cancer A549 cells) | Downregulation of YAP/ILK axis | Suppressed EMT and metastasis | [76] |
| Myricetin | Radioresistant lung cancer A549-IR cells | Suppressed MMP-2 and MMP-9 through the inhibition of FAK-ERK; decreased Slug | Inhibited invasion and migration | [147] |
| Myricetin | Cholangiocarcinoma KKU-100 cells | Suppressed STAT3 and its target genes ICAM-1, MMP-9, iNOS, and COX-2 | Inhibited cytokine-induced migration and invasion | [148] |
| GL-V9 | Colorectal cancer HCT116 and SW480 cells | Reduced MMP-2 and MMP-9; inhibited PI3K/AKT | Suppressed invasion and migration | [149] |
| Baicalein | Breast cancer model in vitro and in vivo | Inhibited STAT3 and IL-6 | Reduced metastatic potential | [150] |
| Chrysin and daidzein | Colorectal cancer induced by subcutaneous injection of DMH in male albino rats | Decreased CXCL1 and MMP-9 | Suppressed metastasis and angiogenesis | [151] |
| Chrysin | Cervical cancer HeLa cells co-administered with TNF-α and TGF-β | Blocked the NF-κB/Twist axis | Inhibited pro-inflammatory cytokine-induced EMT phenotype and CSC-like features | [142] |
| Tangeretin | Breast cancer MDA-MB-231 and MCF-7 cells | Suppressed STAT3 and reduced the level of Sox2; reduced transcript levels of stem cell marker genes (Oct3/4, Sox2, Nanog) | Inhibited breast CSCs | [152] |
| 8-Bromo-7-methoxychrysin | LCSLC in vitro | Reversed M2 polarization of TAMs (inhibition of NF-κB) | Disrupted the interaction of LCSLCs and TAMs | [153] |
| Scutellariae Radix extract | LPS pre-treated cultured RAW 264.7 macrophages | Decreased IL-1β, IL-6, TNF-α, NF-κB, Cox-2, iNOS, and VEGF | Suppressed inflammation-induced angiogenesis | [154] |
| Luteolin | Melanoma A375 and B16-F10 cells | Modulated EMT markers (increased E-cadherin and decreased N-cadherin and vimentin); decreased p-AKT, HIF-1α, VEGF-A, p-VEGFR-2, MMP-2, and MMP-9 | Suppressed HIF-1α/VEGF signaling–mediated EMT and angiogenesis (anti-metastatic effects) | [155] |
| EGCG, silibinin | HUVECs co-cultured with lung cancer A549 cells | Suppressed migration of endothelial and lung tumor cells; downregulated VEGF, VEGFR2, and pro-angiogenic members of the miR-17-92 cluster | Anti-angiogenic efficacy | [156] |
| WCE | Prostate cancer PC-3 and DU145 xenografts | Suppressed IL-6, CXCL1, and CXCL8 → reduced tumor-elicited infiltration of MDSCs, TAMs, and endothelial cells; inhibited STAT3 activation in MDSCs | Inhibited angiogenesis and metastasis | [157] |
| EGCG | Murine 4T1 model of breast cancer | Decreased accumulation of MDSCs; increased CD4+ and CD8+ T cells | Attenuated immunosuppression | [78] |
| Limonin | Balb/c model of colorectal carcinogenesis | Reduced TNF-α; promoted immunophenotyping of CD8, CD4, and CD19 lymphocytes | Decreased inflammation; enhanced immune responses | [158] |