Table 2.
In vitro experimental evidence of ellagic acid (EA) therapeutic potential.
| Formulation | Concentration | Biological Effect | Experimental Model | Reference |
|---|---|---|---|---|
| Pure EA | 30 µg/mL; 7.5–37.5 µg/mL | Growth inhibition | Human colon cancer cell lines: SW480, HCT-116 | [28,32] |
| 6–36 µg/mL | Cell cycle arrest in: G2/M phase | Human colon HCT-15 cancer cell line | [31] | |
| Pomegranate leaf extract | 6.25–200 µg/mL | Human NSCLC A549 and H1299 cell lines; mouse Lewis lung carcinoma LL/2.cell line | [74] | |
| Pure EA | 0.3–15 µg/mL; 1.5–22.5 µg/mL | G0/G1 phase | Human bladder cancer T24 and TSGH8304 cell lines | [93,94] |
| 3–30 µg/mL | G1 phase | Human ovarian carcinoma ES-2, PA-1 cell lines | [107] | |
| 6 µg/mL | Human osteosarcoma Saos-2, MG63 cell lines | [124] | ||
| 15 µg/mL | Human melanoma 1205Lu, WM852c, A375 cell lines | [82] | ||
| 1.5–6 µg/mL | Human NSCLC A549 cell line | [75] | ||
| 15–30 µg/mL | G1/S phase | Human hepatocarcinoma HepG2 cell line | [101] | |
| 4.5–18 µg/mL | S phase | Human glioblastoma U251, U87, U118 cell lines | [119] | |
| Human prostate cancer PC-3 and DU-145 cell lines | [56] | |||
| 0.3–9 µg/mL; 6–36 µg/mL; 7.5–37.5 µg/mL | Apoptosis induction, via intrinsic apoptotic pathway activation | Human colon cancer cell lines: Caco-2; HCT-15; HCT-116 | [30,31,32] | |
| 3–30 µg/mL | Human ovarian carcinoma ES-2, PA-1 cell lines | [107] | ||
| 15–30 µg/mL | Human glioblastoma U251, U87, U118 cell lines | [119] | ||
| 7.5–30 µg/mL | Human melanoma 1205Lu, WM852c, A375 cell lines | [82] | ||
| 15–45 µg/mL | Human oral carcinoma HSC-2 cell line | [112] | ||
| 0.3–15 µg/mL; 1.5–22.5 µg/mL | Human bladder cancer T24 and TSGH8304 cell lines | [93,94] | ||
| 3–30 µg/mL; 0–30 µg/mL; 4.5–18 µg/mL | Human prostate cancer PC-3, LNCaP, DU-145 cell lines | [56,57,58,59] | ||
| Pomegranate leaf extract | 6.25–200 µg/mL | Human NSCLC A549 and H1299 cell lines; mouse Lewis lung carcinoma LL/2 cell line | [74] | |
| Pure EA | 30 µg/mL | Inhibition of tumour cell migration, invasion, metastasis, due to MMP-2, MMP-9, VEFGs downregulation | Human colon cancer Caco-2 cell line | [30] |
| 6 µg/mL | Human osteosarcoma Saos-2 and MG63 cell lines | [124] | ||
| Pomegranate juice; EA; Lutheolin | 5–10%; 5–15 µg/mL; 5–15 µg/mL | Human ovarian cancer A2780 cell line | [109] | |
| 3–9 µg/mL | Human bladder cancer cell lines: T24, UMUC3,5637, HT-1376 | [84] | ||
| Pure EA | 4 µg/mL; 7.5–30 µg/mL | Human PC-3 and rat PLS-10 prostate cancer lines | [60,61] | |
| 6.25–200 µg/mL | Human NSCLC H1299 cell line | [74] | ||
| 3 µg/mL | Enhanced sensibility to radiotherapy | Human breast cancer MCF7 cell line | [52] | |
| 3 µg/mL | Human hepatocarcinoma HepG2 cell line | [102] | ||
| Pomegranate juice; Lutheolin+EA+ punicic acid | 1–5%; 1–8 µg/mL; 4–8 µg/mL | Inhibition of genes promoting tumour cell migration and up-regulation of genes promoting cell adhesion | Human breast cancer MDA-MB-231 and MCF7 cell lines | [51] |
| Pure EA | 7.5–15 µg/mL | Human prostate cancer DU145, PC3, LNCaP cell lines | [62,63] | |
| 30 µg/mL | DNA damage, p53 and p21 activation, IGF-II downregulation; Increased production of ROS | Human colon cancer SW480 and HCT-115 cell lines | [28,31] | |
| 3–30 µg/mL | Human ovarian carcinoma ES-2 and PA-1 cell lines | [107] | ||
| 0.3–15 µg/mL | Human bladder cancer T24 and TSGH8301 cell lines | [82,83] | ||
| 30–36 µg/mL | Neuroendocrine differentiation of cancer cells | Human prostate cancer LnCap and DU145 cell lines | [57] | |
| 3–30 µg/mL | Overcome of TKI-resistance | Human NSCLC HCC827 clones | [76] | |
| 0.96–3 µg/mL | Enhanced sensibility to doxorubicin and cisplatin | Human ovarian cancer ES-2, PA-1, A2780 cell lines | [107,108] | |
| 1.5–18 µg/mL | Enhanced sensibility to mitomycin C | Human bladder cancer T24, UMUC3, 5637, HT-1376 cell lines | [84] | |
| 0.3–30 ng/ml; 0.3 µg/mL–3 ng/mL | Estrogenic; anti-estrogenic activity | Human breast cancer MCF-7 cell line | [42,43] | |
| 3–9 µg/mL; 15 µg/mL | Modulation of TGF-β; Smads and PI3K pathways | Human breast cancer MCF-7 cell line | [45,46,47] | |
| 6–18 µg/mL | Down-regulation of PDL-1 | Human bladder cancer T24, UMUC3,5637, HT-1376 cell lines | [84] | |
| 30 µg/mL | Changes in gene expression | Human colon cancer HCT-116 and Caco-2 cell lines | [32,33] | |
| EA; metabolites UroA and UroB | 3 µg/mL; 12 µg/mL | Human prostate cancer LNCaP cell line | [58] | |
| EA, UroA, UroB, 8-OMe-urolithin A | 30 µg/mL | Antiproliferative effect by p38-MAPK and/or c-Jun medicated caspase-3 activation | Human bladder cancer T24 and UMUC3 cell lines | [96,97] |
| EA and UroA, UroB, UroC | 0.3–36 µg/mL | Cell cycle arrest, increasing apoptotic cell death and inhibiting PI3K/Akt and MAPK signalling pathway | Human NSCLC A549 cell line | [75] |
| UroA and UroB | 0.15–22.5 µg/mL | Inhibition of viability and tysosinase activity | Murine melanoma B16 cell line | [88] |
| UroA | 0.075–60 µg/mL | Estrogenic activity | Human breast cancer MCF-7 cell line | [44] |
| EA derivative 4,4′-DiOMEA | 3 µg/mL | Inhibition of cell proliferation, enhancing sensibility to 5-FU and 5’DFUR | Human colon cancer SW-620, SW-620-5FuResistant, HT-29, Caco-2, SW-480 cell lines | [36,37] |
| EA-encapsulated chitosan nanoparticles | 0.03–15 µg/mL | Antiproliferative/apoptotic effects | Human oral cancer KB cell line | [113] |
| 3–30 µg/mL | Human hepatocarcinoma HepG2 cell line | [103] | ||
| Chitosan-EA films | 0.3–15 µg/mL | Human melanoma WM115 cell line | [90] | |
| EA-peracetate | 0.2–100 µg/mL | Murine melanoma B16 cell line | [89] | |
| Pomegranate extract | 0.5–1% (w/v); 5–200 µg/mL | Murine breast cancer WA4 cell line | [48] | |
| Human breast cancer MCF-7 cell line | [49] | |||
| T. chebula fruit extract | EA IC50 = 23.5 µg/mL | Human MCF-7 and mouse S115 breast cancer cell lines, human osteosarcoma HOS-1 cell line, human prostate cancer PC-3 cell line | [41] |