Table 3.
Molecular actions of chlorogenic acid on various forms of cancer.
| No | Types of Cancer | Details of Assay | Application | Analytical Findings | Ref. |
|---|---|---|---|---|---|
| 1 | Lung cancer | Male BALB/c nude mice and human lung cancer A549 cell | In-vivo and in-vitro | Effectively diminishes the binding of annexin A2 to p50 subunits, and expression of downstream anti-apoptotic genes cIAP1 and cIAP2 via NF-kB signaling pathway. | [121] |
| A549 human lung cancer cell | In-vitro | Attenuates cell proliferation, expression levels of BCL2, and stem cell-related markers (SOX2, POU5F1, and NANOG); triggered JNK and p38 MAPK gene expression; and elevated expressions of CASP3, BAX, and annexin V. | [122] | ||
| Human lung cancer A549 cell | In-vitro | Induces DNA damage, high level of topoisomerase-I and topoisomerase-II DNA complexes in cells. | [123] | ||
| Male BALB/c nude mice and human lung cancer A549 cell | In-vivo and In-vitro | Suppresses the expressions of VEGF, HEY1, HES1, Delta4, cell proliferation, and mRNA of Notch1; improved p-AKT, p-PTEN and PTEN in tumor tissues. | [124] | ||
| Human lung cancer A549 cell | In-vitro | Down-regulates migration of A549 cells, Ac-NF-kB expression, matrix metalloproteinase-2 (MMP-2) and histone deacetylase-6 (HDAC6) activities. | [125] | ||
| 2 | Breast cancer | Mouse 4T1 breast cancer cell | In-vivo | Hampers the expression of CD206 triggered by IL-13, M2 related gene Ym1 and metastatic nodes in the lungs. | [126] |
| Mouse 4T1 breast cancer cell | In-vivo | Hinders the viability, proliferation, migration and invasion in breast cancer cells, NF-kB p65 nuclear translocation, EMT and NF-kB mechanism | [127] | ||
| Mouse 4T1, EMT6, BT-549, and MDA-MB-231 cell and EMT6 xenograft model | In-vivo and In-vitro | Inhibits cell viability, tumor volume and weight, and expressions of EGF, TGF-β, VEGF, CD34, and IL-10; activates apoptosis in a dose dependent manner. | [128] | ||
| MCF-7 breast cancer cell | In-vitro | Promotes abundant nuclear condensation, morphological changes, alters the expression of p53 and caspase-3 mRNA, and diminished Bcl-2 protein as well as the acidic autophagosomal vacuolization. | [129] | ||
| Mouse 4T1 breast cancer cell | In-vivo | Decreases tumor weight and volume, elevates Bcl-2/Bax expression ratio, caspase-3 and p53 gene expression. | [130, 131] | ||
| MCF-7 breast cancer cell | In-vitro | Up-regulates STAT5B protein level and inhibits cyclin D1 levels. | [132] | ||
| 3 | Colon cancer | HT-29 colon cancer cell | In-vitro | Suppresses cell viability, G1 cell cycle arrest and apoptotic cell death. | [132] |
| CT-26 colon cancer cell | In-vitro | Decreases ERK phosphorylation, NF-kB and AP-1 transactivation, mitogen-activated MEK1 and TOPK activities, and EGF-, TPA-, and H-Ras-triggered neoplastic transformation of JB6 P+ cells. | [133] | ||
| Human HT-29 colon cancer Caco-2 cell | In-vitro | Reduces cell proliferation, and activated caspase-3 and cell cycle arrest at the S-phase | [134] | ||
| Human HT-29 colon adenocarcinoma cell | In-vitro | Potentiates specific changes in the cell cycle, rate of apoptosis and repressed HT-29 cell viability. | [135] | ||
| Human HCT-15 and CO-115 colon adenocarcinoma cells | In-vitro | Inhibits cell proliferation, BRAF, phospho-ERK expression, Akt phosphorylation, and activated caspase-dependent apoptosis, p38, JNK, S and G2/M phase cell cycle arrest. | [136] | ||
| N-methyl-N-nitro-N-nitrosoguanidine induced male wistar mice | In-vivo | Significantly alleviates the level of expressions of malondialdehyde, glutathione, cyclooxygenase-2, α-tocopherol and DNA damage intensity. | [137] | ||
| Human HCT-116 and HT-29 colon cancer cells | In-vitro | Attenuates the activation of extracellular signal related kinase, cell viability, and triggered S-phase cell cycle arrest and ROS production. | [138] | ||
| Human HCT-116 colon adenocarcinoma cell | In-vitro | Activates apoptosis via induction of PARP-1 cleavage, DNA fragmentation, caspase-9, decreases anti-apoptotic protein Bcl-2 and increased pro-apoptotic protein Bax. | [139] | ||
| 4 | Liver cancer | HepG2 human hepatocarcinoma cell | In-vitro | Enhances the apoptotic action of regorafenib via triggering pro-apoptotic annexin V, Bax, and caspase 3/7, and suppressed anti-apoptotic Bcl2 and Bcl-xL, cell motility, MAPK and PI3K/Akt/mTOR mechanism. | [140] |
| HepG2 and Hep3B human hepatocarcinoma cells | In-vitro | Causes cell proliferation, ERK1/2 inactivation and promotes production of reactive oxygen species (ROS). | [141] | ||
| HepG2 cell and HepG2 xenograft tissue | In-vitro | Down-regulates the expressions of MMP-2, MMP-9, cell proliferation, and triggered the inactivation of ERK1/2. | [142] | ||
| HepG2 human hepatocarcinoma cell | In-vitro | Inhibits the cellular proliferation, colony formation, invasion, and metastasis, MMP-2 and MMP-9 expressions, up-regulates p53 and p21 activity, and inactivates ERK1/2. | [143] | ||
| HepG2 human hepatocarcinoma cell | In-vitro | Promotes nuclear translocation of Nrf2, ARE reporter gene activity, and downstream antioxidant proteins (involving sestrin2, hemeoxygenase-1, glutamate cysteine ligase and NAD(P)H quinone oxidoreductase-1) | [144] | ||
| 5 | Blood cancer | Human U937 leukemia cell | In-vitro | Activates apoptosis via increasing ROS production, expression of caspase-3, 7, 8, 9, and decreasing the mitochondrial membrane potential (ΔΨm). | [145] |
| Human HL-60 leukemia cell | In-vitro | Increases the level of apoptosis in a dose-dependent manner, and halts G0/G1 phase cell cycle and proliferation. | [146] | ||
| Bcr-Abl(+) chronic myeloid leukemia and K562 xenograft nude rats | In-vivo | Potentiates death receptor DR5; triggered deposition of intracellular reactive oxygen species, loss of mitochondrial membrane potential, caspase-8 cleavage, and partially impaired apoptosis. | [147] | ||
| Bcr-Abl(+) chronic myeloid leukemia and K562 xenograft nude rats | In-vivo | Suppresses Bcr-Abl kinase resulting to activation of p38 MAPK. | [148] | ||
| Human K-562 and CCRF-CEM and A549 lung adenocarcinoma cells | In-vitro | Attenuates cell viability in a concentration dependent manner, and decreases mitochondria membrane potential via up-regulating mitochondrial DNA lesions in ND1 and ND5 genes and causing nuclear DNA damage in TP53 gene. | [149, 150] | ||
| 6 | Brain cancer | Human glioma cell | In-vitro | Reduces cell proliferation and triggered apoptosis in a dose dependent manner. Promotes the pro-apoptotic Bax protein, p53 protein level and inhibits Bcl-2 protein and mitochondrial membrane potential. | [151, 152] |
| Human glioma cell | In-vitro | Hinders colony formation. Activates apoptosis via enhancing ROS leading to a disruption of mitochondrial membrane potential. Improved S and G2/M phase cell cycle, and mRNA levels of the apoptotic factors such as p53, caspase-3, caspase-8, caspase-9, Tp53, and Bax. | [153, 154] | ||
| U87MG and patients-derived IV grade glioma cells | In-vitro | Alleviates UHRF1 and DNMT1. Activates double strand DNA damage via promoting the number of phosphorylated H2A.X and cleaved PARP1. | [155, 156] | ||
| 7 | Bone cancer | U2OS, Saos-2, and MG-63 OS cells | In-vitro | Diminishes cell proliferation via activation of apoptosis, inhibits ERK1/2, and altered cell cycle. | [157] |
| 8 | Skin cancer | Human melanoma (SK-MEL-2) cell | In-vitro | Mediates apoptosis via suppression of MEK/ERK mechanism and enhanced caspase-3 activity. | [158] |
| 9 | Kidney cancer | A498 human kidney cancer cell | In-vitro | Activates proliferation via induction of caspase protein and up-regulating pro-apoptotic protein Bax ratio to anti-apoptotic protein Bcl-2. | [159] |
| 10 | Pancreatic cancer | Human pancreatic cancer PANC-1 cell | In-vitro | Hampers cellular proliferation, causes cell cycle arrest, triggers apoptosis and loss in the mitochondrial membrane potential. | [160] |