TABLE 3.
Potential anticancer effects and related mechanisms of action of naringin based on in vitro studies.
| Cancer type | Cell type | Conc | Source | Purity (%) | Quality control reported? (Y/N) | Duration | Anticancer effects | References |
|---|---|---|---|---|---|---|---|---|
| Bladder | T24 and 5,637 cell lines | 50–150 μM | Wako pure chemical Industries, ltd. (Osaka, Japan) | ND | Y | 24 h | ↓Cell proliferation, ↓cell viability, ↓cell growth, ↑cell cycle arrest, ↑p21WAF1, ↑Ras, ↑Raf | Kim et al. (2008) |
| Bladder | TCC cell line | 0.3–5 μM | Merck Chemical Co. (Darmstadt, Germany) | ND | Y | 24–48 h | ↓Cell proliferation, ↓cell viability | Karami et al. (2018) |
| Bladder | TCC cell line | 75 μg/ml | Sigma-Aldrich (Munich, Germany) | ND | Y | 24–72 h | ↓Cell proliferation, ↓cell viability | Oršolić et al. (2009) |
| Blood (leukemia) | HL-60, Kasumi-1, and K562 cell lines | 0.125–2 mg/ml | China Institute of drugs and Bioproducts (Beijing, China) | ND | Y-HPLC | 24–48 h | ↓Cell proliferation, ↑apoptosis, ↓Mcl-1 | Dai et al. (2017) |
| Blood (leukemia) | U937 cell line | 50–500 μM | Sigma-Aldrich (Lyon, France) | (90%) | Y | 24 h | ↓Cell proliferation, ↓cell growth, ↑cell death | Jin et al. (2009) |
| Blood (leukemia) | THP-1 cell line | 50–400 μM | Gibco BRL (Gaithersburg, MD, United States) | ND | Y | 48 h | ↓Cell proliferation, ↓cell viability | Park et al. (2008) |
| Blood (leukemia) | HL-60 and THP-1 cell lines | 40–80 μM | Sigma-Aldrich (Lyon, France) | ND | Y | 6–24 h | No effect | Chen et al. (2003) |
| Blood (leukemia) | K562 cell line | 5–500 μM | Quinabra Company (São José dos Campos, Brazil) | ND | Y | 24–72 h | ↓Cell number, ↓cell growth, ↑cell death, ↓DPPH | Pereira et al. (2007) |
| Blood (leukemia) | K562 cell line | 1–100 μM | Fluka chemie GmbH (Buchs, Switzerland) | (≥95%) | Y- TLC and HPLC | 20–100 h | ↓VEGF | Mellou et al. (2006) |
| Blood (lymphoma) | P-388D1, L-1210 cell lines | 1–2 mM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 12 h | ↑Cytotoxic activity, ↑anti-platelet aggregation activity, ↑trypsin inhibition | Kim et al. (1998) |
| Blood (lymphoma) | Raji cell line | 10–1,000 μM | Extrasynthese-Genay (Lyon, France) | ND | Y | 24 h | ↓Cell proliferation, ↓cell growth | Ramanathan et al. (1992) |
| Brain | U-87cell line | 5–30 μM | Sigma-Aldrich (Lyon, France) | (98%) | Y | 24–48 h | ↓Cell proliferation, ↓cell viability, ↓cell invasion, ↓tubulogenesis | Aroui et al. (2020) |
| Brain | U87 and U251 cell lines | 10–40 μM | Invitrogen (Carlsbad, CA, USA) | ND | Y | 12–48 h | ↓Cell proliferation, ↓FAK/cyclin D1 pathway, ↑apoptosis, ↓cell invasion, ↓metastasis, ↓migration, ↓FAK/MMPs pathway, ↓kinase activity of FAK | Li et al. (2017) |
| Brain | U373 and U87 cell lines | 5–100 μM | Sigma-Aldrich (Lyon, France) | ND | Y | 12–24 h | ↓Cell growth, ↓cell viability, ↓migration, ↓cell invasion, ↓MMP-9, ↓MMP-2, ↑MAPK signaling pathways, ↓metastasis | Aroui et al. (2016a) |
| Brain | U251 cell line | 5–60 μM | Sigma-Aldrich (Lyon, France) | (98%) | Y | 24 h | ↓Cell proliferation, ↓cell viability, ↓cell invasion, ↓migration, ↓ MMP-9, ↓MMP-2, ↑TIMP-2, ↑TIMP-1, ↓p38 signal transduction pathways | Aroui et al. (2016b) |
| Brain (Glioma) | U343 and U118 cell lines | 0.1–100 μM | Sigma-Aldrich (Steinheim, Germany) | ND | Y | 24 h | ↓VEGF | Schindler and Mentlein (2006) |
| Breast | MCF-7 cell line | 50–400 μg/ml | Sigma-Aldrich (Berlin, Germany) | ND | Y-HPLC | 48–72 h | ↓Cell proliferation, ↓cell growth, ↑apoptosis | Elansary et al. (2020) |
| Breast | MCF7 cell line | 5 μM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y-HPLC | 12–48 h | ↓Cell proliferation, ↓cell viability | Puranik et al. (2019) |
| Breast | MCF7 and HCT116 cell lines | 0.78–100 μg/ml | Purified by Basta et al., 2020 | ND | Y-TLC | 48 h | ↓Cell proliferation, ↓cell viability | Basta et al. (2020) |
| Breast | MCF7 cell line | 0.78–100 μg/ml | Purified by Atta et al., 2019 | ND | Y-TLC | 48 h | ↓Cell viability, ↓cell growth, ↑apoptosis | Atta et al. (2019) |
| Breast | MCF-7 cell line | 200 μM | Sigma-Aldrich (St. Louis, MO, United States) | (≥95%) | Y | 72 h | ↓Cell proliferation, ↓cell viability, ↑apoptosis | Fazary et al. (2017) |
| Breast | MCF7 cell line | 0.3–5 μM | Merck Chemical Co. (Darmstadt, Germany) | ND | Y | 24–48 h | ↓Cell proliferation, ↓cell viability | Karami et al. (2018) |
| Breast | MCF7 cell line | 20–100 μM | Sigma-Aldrich (St. Louis, MO, USA) | (97%) | Y-HPLC | 1–48 h | ↓Cell proliferation, ↓cell viability | Selvaraj et al. (2014) |
| Breast | MCF-7 and MDA-MB-231 cell lines | 5–100 μM | Sigma-Aldrich (Poznań, Poland) | ND | Y | 24–48 h | ↓Cell viability, ↑cell cycle arrest, ↑apoptosis | Kabała-Dzik et al. (2018) |
| Breast | CMT-U27 cell line | 20–1,000 μM | Sigma-Aldrich Chemical Co. (Steinheim, Germany) | ND | Y | 48 h | ↓Cell proliferation, ↓cell viability | Özyürek et al. (2014) |
| Breast | MDA-MB-231, MDA-MB-468, and BT-549 cell lines | 50–200 μM | Sigma-Aldrich (St. Louis, MO, USA) | (≥95%) | Y-HPLC | 24–48 h | ↓Cell proliferation, ↓cell growth, ↑cell cycle arrest, ↓cell viability, ↑apoptosis, ↓β-catenin pathway | Li et al. (2013a) |
| Breast | Ehrlich ascites tumor cells | 5–100 μM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 3–24 h | ↑Tumor cell death, ↓tumor cell growth | Menon et al. (1995) |
| Breast | MDA-MB-231 cell line | 0.1–100 μM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 24 h | ↓VEGF | Schindler and Mentlein (2006) |
| Cervical | C33A, SiHa, and HeLa cell lines | 10–10,000 μM | Sigma-Aldrich (St. Louis, MO, USA) | (≥95%) | Y-HPLC | 24 h | ↓Cell viability, ↑cell cycle arrest, ↑apoptosis, ↓Wnt/β-catenin pathway | Chen et al. (2020) |
| Cervical | SiHa cell line | 250–2000 μM | Sigma–Aldrich (St. Louis, MO, United States) | ND | Y | 24–48 h | ↓Cell proliferation, ↓cell viability, ↑cell cycle arrest, ↑apoptosis, ↑caspases, ↑p53, ↑Bax, ↑Fas | Ramesh and Alshatwi (2013) |
| Cervical | HeLa cell line | 200–2000 μM | Sigma-Aldrich (St. Louis, MO, United States) | ND | Y | 24 h | ↓Cell proliferation, ↓cell growth, ↑apoptosis | Liu et al. (2017) |
| Cervical | HeLa cell line | 200–3200 μM | Nacalai tesque (Kyoto, Japan) | ND | Y | 48 h | ↓Cell growth, ↑apoptosis, ↓NEU3, ↑EGFR/ERK signaling | Yoshinaga et al. (2016) |
| Cervical | HeLa cell line | 10–1,000 μM | Extrasynthese-Genay (Lyon, France) | ND | Y | 24 h | ↓Cell proliferation, ↓cell growth | Ramanathan et al. (1992) |
| Cervical | HeLa cell line | 50–400 μg/ml | Sigma-Aldrich (Berlin, Germany) | ND | Y-HPLC | 48–72 h | ↓Cell proliferation, ↓cell growth, ↑apoptosis | Elansary et al. (2020) |
| Cervical | HeLa cell line | 200–1,500 μmol/L | Sigma-Aldrich (St. Louis, MO, United States) | ND | Y | 3–48 h | ↓Cell viability, ↓cell growth, ↑apoptosis, ↓NF-κB/COX-2-caspase-1 pathway | Zeng et al. (2014) |
| Colon | HT-29 cell line | 50–400 μg/ml | Sigma-Aldrich (Berlin, Germany) | ND | Y-HPLC | 48–72 h | ↓Cell proliferation, ↓cell growth, ↑apoptosis | Elansary et al. (2020) |
| Colon | CT26 cell line | 1–100 μg/ml | Purified by Zhou et al., 2018 | ND | Y- HPLC | ↓Cell proliferation, ↓cell viability, ↑apoptosis | Zhou et al. (2018) | |
| Colon | SW480 cell line | 12.5–200 μM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 12–48 h | ↓Cell proliferation, ↓cell viability | Chidambara Murthy et al. (2012) |
| Colorectal | HCT116 and SW620 cell lines | 6–25 μg/ml | Beijing Solarbio Science and Technology Co., Ltd (Beijing, China) | ND | Y | 12–72 h | ↓Cell proliferation, ↑apoptosis, ↓PI3k/Akt/mTOR pathway | Cheng et al. (2020) |
| Colon | Colo 205 and Colo 320 cell lines | 4–10 μg/ml | Purified by Ugocsai et al. (2005) | ND | Y | 24 h | ↑Apoptosis | Ugocsai et al. (2005) |
| Colon | COLO 320HSR, COLO 205, and HT 29 cell lines | 200 μM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 24 h | No effect | Shen et al. (2004) |
| Colon | HT29 cell line | 10–250 μg/ml | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y-HPLC and mass spectrometer | 24–48 h | ↓Cell proliferation, ↓cell growth | Ferreira et al. (2013) |
| Colon | HCT116 cell line | 200 μM | Sigma Aldrich (St. Louis, MO, United States) | (≥95%) | Y | 72 h | ↓Cell proliferation, ↓cell viability, ↑apoptosis | Fazary et al. (2017) |
| Colon | HCT116 cell line | 0.78–100 μg/ml | Purified by Basta et al., 2020 | ND | Y-TLC | 48 h | ↓Cell proliferation, ↓cell viability | Basta et al. (2020) |
| Colon | SNU-C4 cell line | 1–2 mM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 12 h | ↑Cytotoxic activity, ↑anti-platelet aggregation activity, ↑trypsin inhibition | Kim et al. (1998) |
| Colorectal | Caco-2 cell line | 10–1,000 μM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 24 h | ↓Cell proliferation, ↓cell growth, ↓cell viability ↓GLO-I activity | Yadav et al. (2016) |
| Colon | HT-29 and Caco-2 cell lines | 10–60 μM | Fluka Chemika-BioChemika (New York, USA) | (>95%) | Y | 24–48 h | No effect | Kuo (1996) |
| Esophageal | YM1 cell line | 300 μM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 24 h | ↓Cell proliferation, ↓cell viability | Tajaldini et al. (2020) |
| Head and Neck (laryngeal) | HEp2 cell line | 3.8–500 μM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 72 h | ↓Cell viability, ↓lipid peroxidation, ↑CYP1A1 | Durgo et al. (2007) |
| Liver | HepG2 cell line | 12.5 μM–3.2 mM | Sigma–Aldrich (St. Louis, MO, United States) | (≥95%) | Y-HPLC | 48 h | ↓Cell viability, ↓cell growth, ↑apoptosis | Elsawy et al. (2020) |
| Liver | HepG2 cell line | 5 μM | Sigma-Aldrich (St. Louis, MO, United States) | ND | Y | 24 h | ↓Cell proliferation, ↓cell viability | Syed et al. (2020) |
| Liver | HepG2 cell line | 10–40 μM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 24–72 h | ↓Cell proliferation, ↑apoptosis, ↑Bax, ↓Bcl-2, ↑miR-19b | Xie et al. (2017) |
| Liver | HepG2 cell line | 50–250 μg/ml | Sigma-Aldrich (St. Louis, MO, United States) | ND | Y | 24 h | ↓Cell proliferation, ↓cell viability, ↓cell growth, ↑apoptosis | Banjerdpongchai et al. (2016a) |
| Liver | HepG2 cell line | 100 μg/ml | Sigma-Aldrich (St. Louis, MO, United States) | ND | Y | 24 h | ↓Cell proliferation, ↑apoptosis, ↑Bax, ↑Bak, ↓Bcl-xL, ↑tBid | Banjerdpongchai et al. (2016b) |
| Liver | HepG2 cell line | 1–100 μg/ml | Purified by Zhou et al., 2018 | ND | Y- HPLC | ↓Cell proliferation, ↓cell viability, ↑apoptosis | Zhou et al. (2018) | |
| Liver | HepG2, Huh-7, and HA22T cell lines | 25–100 μM | Sigma–Aldrich (St. Louis, MO, United States) | (>98%) | Y | 8–24 h | ↓Cell invasion, ↓migration, ↓metastasis, ↓MMP-9, ↓PI3K/Akt, ↓MAPK, ↓IκB | Yen et al. (2015) |
| Liver | HepG2 cell line | 10–250 μg/ml | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y-HPLC and mass spectrometer | 24–48 h | ↓Cell proliferation, ↓cell growth | Ferreira et al. (2013) |
| Liver | HepG2, MCF-7, and HCT116 cell lines | 200 mM | Sigma-Aldrich (St. Louis, MO, United States) | (≥95%) | Y | 72 h | ↓Cell proliferation, ↓cell viability, ↑apoptosis | Fazary et al. (2017) |
| Liver | HA22T and SK-Hep1 cell lines | 10–100 μM | Aldrich chem. Co. (Milwaukee, WI, United States) | ND | Y | 24 h | ↓Cell viability, ↓cell growth | Hsiao et al. (2007a) |
| Liver | HepG2 cell line | 1–2 mM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 12 h | ↑Cytotoxic activity, ↑anti-platelet aggregation activity, ↑trypsin inhibition | Kim et al. (1998) |
| Liver | Hepa-1c1c7 cell line | 50–100 μM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 72 h | No effect | Campbell et al. (2006) |
| Lung | A549 cell line | 3–1,000 μM | Purified by Nie et al., 2012 | (>98.3%) | Y-determined by peak area normalization | 24–96 h | ↓Cell proliferation, ↓cell viability | Nie et al. (2012) |
| Lung | A549 and LLC cell lines | 10–100 μM | Aldrich chem. Co. (Milwaukee, WI, United States) | ND | Y | 24 h | ↓Cell viability, ↓cell growth | Hsiao et al. (2007a) |
| Lung | H69AR cell line | 6–25 μg/ml | ND | ND | ND | 24 h | ↓Cell proliferation, ↓cell growth, ↑apoptosis, ↑miR-126, ↓PI3K, ↓p-Akt, ↓p-mTOR, ↓VCAM-1, ↓NF-κB, ↓PI3K/Akt/mTOR pathway | Chen et al. (2018) |
| Lung | A549 cell line | 10–50 μM | Aldrich chem. Co. (Milwaukee, WI, United States) | ND | Y | 24 h | ↓Cell viability, ↓cell invasion, ↓cell-matrix adhesion, ↓cellular motility | Hsiao et al. (2007b) |
| Lung | A549 cell line | 1–2 mM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 12 h | ↑Cytotoxic activity, ↑anti-platelet aggregation activity, ↑trypsin inhibition | Kim et al. (1998) |
| Lung | A549 cell line | 10–120 μg/ml | Sigma-Aldrich, (St. Louis, MO, United States) | ND | Y | 6–24 h | ↓Cell proliferation, ↓cell viability, ↑apoptosis | Garcia et al. (2019) |
| Lung | A549 cell line | 0.78–100 μg/ml | Purified by Atta et al., 2019 | ND | Y-TLC | 48 h | ↓Cell viability, ↓cell growth, ↑apoptosis | Atta et al. (2019) |
| Lung | HeLa and A549 cell lines | 200–3200 μM | Nacalai Tesque, Inc. (Kyoto, Japan) | ND | Y | 48 h | ↓Cell growth, ↑apoptosis, ↓NEU3, ↑EGFR/ERK signaling | Yoshinaga et al. (2016) |
| Neuroblastoma | SH-SY5Y cell line | 1–10 μM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 24 h | ↓Cell viability, ↑cell death | Kim et al. (2009) |
| Ovarian | SKOV3/CDDP cell line | 10–40 μmol/L | Institute of pharmacology at Nanchang university (Nanchang, China) | ND | Y | 48 h | ↓NF-κB, ↓P-gp | Zhu et al. (2018) |
| Ovarian | SKOV3/CDDP cell line | 10–40 μmol/L | Shandong Qilu Pharmaceutical Co., Ltd. (Shandong, China) | ND | Y | 48 h | ↓NF-κB, ↓COX-2 | Zhu et al. (2017) |
| Ovarian | OVCAR-3 cell line | 5–160 μM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 24 h | No effect | Luo et al. (2008) |
| Prostate | PC-3 and LNCaP cell lines | 2.5–300 μM | Selleck (Maple Valley, WA, USA) | ND | Y | 24–48 h | ↓Cell growth, ↓migration, ↓cell invasion, ↑apoptosis, ↑Bax, ↓p-↓STAT3, ↓survivin, ↓Bcl-2, ↓p-Akt | Wu et al. (2019) |
| Prostate | PC3, DU145, and LNCaP cell lines | 3.9–500 μM | Sigma-Aldrich (St. Louis, MO, United States) | ND | Y | 72 h | ↓Cell survival, ↓cell viability, ↑apoptosis, ↑cell cycle arrest, ↑PTEN, ↓nuclear factor-κB p50 protein, ↓cell migration, ↓NF-κB signaling | Erdogan et al. (2018) |
| Prostate | DU145 cell line | 50–250 μM | Sigma-Aldrich (Poznan, Poland) | ND | Y | 24 h | ↓Cell proliferation, ↓cell viability, ↓cell number, ↑oxidative stress, ↑apoptosis | Lewinska et al. (2015) |
| Sarcoma (osteosarcoma) | MG63 and U2OS cell lines | 10–20 μmol/L | Beyotime Biotechnology (Shanghai, China) | ND | Y | 24 h | ↓Cell proliferation, ↓cell invasion, ↑apoptosis, ↓Zeb1, ↓cell migration, ↑cell cycle arrest | Ming et al. (2018) |
| Sarcoma (osteosarcoma) | MG-63 cell line | 1–100 μg/ml | Purified by Zhang et al., 2018a | ND | Y-HPLC and Mass spectrometry | 24–72 h | No effect | Zhang et al. (2018a) |
| Sarcoma (chondrosarcoma) | JJ012 cell line | 3–30 μM | Sigma-Aldrich (St. Louis, MO, United States) | ND | Y | 24–48 h | ↓Cell invasion, ↓migration, ↓VCAM-1, ↑miR-126 | Tan et al. (2014) |
| Skin (Melanoma) | A375 and A875 cell lines | 10–40 μM | ND | ND | ND | 12–60 h | ↓Cell proliferation, ↓cancer metabolism, ↑cell cycle arrest, ↑apoptosis, ↓cell growth, ↓cell invasion, ↓migration, ↓c-Src | Guo et al. (2016) |
| Skin (Melanoma) | MO4 cell line | 0.5 mM | Provided by dr. J, A. Attaway (department of citrus, state of Florida, United States) | ND | Y- Reversed-phase high-pressure liquid chromatography | 4 days | ↓Invasion | Bracke et al. (1991) |
| Skin (Melanoma) | B16F10 cell line | 5–500 μM | Quinabra Company (São José dos Campos, Brazil) | ND | Y | 24–72 h | ↓Cell number, ↓cell growth, ↑cell death, ↓DPPH | Pereira et al. (2007) |
| Stomach (Gastric) | AGS cell line | 1–3 mM | Sigma-Aldrich (St. Louis, MO, United States) | ND | Y | 3–24 h | ↑ROS, ↑ERK1/2-p38 MAPKs, ↑autophagy cell death | Raha et al. (2020) |
| Stomach (Gastric) | AGS cell line | 10–100 μM | Aldrich Chemical Co. (Milwakee, WI, United States) | ND | Y | 24 h | ↓Cell viability, ↓cell growth | Hsiao et al. (2007a) |
| Stomach (Gastric) | AGS cell line | 1–3 mM | Sigma-Aldrich (St. Louis, MO, United States) | ND | Y | 24–48 h | ↓Cell proliferation, ↓cell growth, ↓PI3K/Akt/mTOR, ↑MAPKs, ↑p21CIPI/WAFI, ↑autophagosome | Raha et al. (2015) |
| Stomach (Gastric) | SNU-1 | 1–2 mM | Sigma-Aldrich (St. Louis, MO, USA) | ND | Y | 12 h | ↑Cytotoxic activity, ↑anti-platelet aggregation activity, ↑trypsin inhibition | Kim et al. (1998) |
| Thyroid | TPC-1 and SW1736 cell lines | 6–25 μg/ml | Beyotime Biotechnology (Shanghai, China) | ND | Y | 24–72 h | ↓Cell proliferation, ↑apoptosis, ↓PI3k/Akt pathway | Zhou et al. (2019) |
Note: A down arrow indicates a reduction or decrease and an up arrow indicates an increase. Bak, Bcl-2 homologous antagonist/killer; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2; Bcl-xL, B-cell lymphoma-extra-large; COX-2, cyclooxygenase- 2; c-Src, proto-oncogene tyrosine-protein kinase Src; DPPH, diphenylpicrylhydrazyl radical; EGFR, epidermal growth factor receptor; ERK, extracellular signal-regulated kinase; FAK, focal adhesion kinase; GLO-I, glyoxalase-I; IκB, inhibitor of NF-κB; MMPs, matrix metallopeptidases; MAPK, mitogen-activated protein kinase; Mcl-1, myeloid cell leukemia 1; miR, microRNA; mTOR, mammalian target of rapamycin; ND, not determined; NEU3, plasma membrane-associated sialidase; NF-κB, nuclear factor-κB; p53, tumor protein p53; p38 MAPKs, p38 mitogen-activated protein kinases; p-Akt, phosphorylated Akt; P-gp, P-glycoprotein; PI3K, phosphatidylinositol-3-kinase; p-mTOR, phosphorylated mammalian target of rapamycin; p-STAT3, phosphorylated signal transducer and activator of transcription 3; ROS, reactive oxygen species; tBid, truncated BH3 interacting domain death agonist; TIMP, tissue inhibitor of metalloproteinase; VCAM-1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor; Zeb1, zinc finger E-box binding homeobox 1.