Table 2.
Modulatory polyphenol impact on signaling pathways in cervical cancer cell lines.
| Polyphenol | Concentration/ Time |
Experimental Model |
↑ Upregulation |
↓ Downregulation |
Final Effect |
Reference |
|---|---|---|---|---|---|---|
| Punicalagin | 10–200 μM 24 to 48 h |
ME-180 HeLa SiHa |
Bax Casp-3, 7, 9 STAT3 pRb |
NF-KB Bcl-2 Cyclin D1 c-myc E6 and E7 |
Inhibition of cell proliferation and induction of apoptosis Cell cycle arrest |
[50,51,52] |
| Punicalin | 100, 500, and 1000 ppm 24, 48, and 72 h |
HeLa | Casp-3 | Bcl-2 | Suppression of cell viability Induction of apoptosis |
[33] |
| Gallic acid | 10–400 μg/mL 30 min to 72 h |
HTB-35 HeLa |
ROS | ADAM17 EGFR p-Akt GSH |
Cell cycle arrest Induction of apoptosis/ necrosis Inhibition of cell migration |
[63,64,65] |
| Ellagic acid | 2.5–30 μM 24, 48, and 72 h |
HeLa SiHa C33A |
STAT3 IGFB7 ROS P53 P21 Bax |
Cyclin E6 |
Inhibition of cell proliferation and induction of apoptosis Cell cycle arrest at G1 phase Suppression of Akt/mTOR pathway Induce DNA damage |
[69,70,71,72] |
| Caffeic acid | 1–100 μM 24 to 48 h |
HeLa SiHa ME180 Caski Z172 |
E2F-1 Casp-3 p53 |
Bcl-2 | Cell cycle arrest at S and G2/M phases | [76,77,78] |
| Chlorogenic acid | IC50 ~ 10(-4) M 24 h |
A431 A431Pt |
___ | ___ | Binds with cisplatin and oxaliplatin to oppose drug resistance | [85,86] |
| Delphinidin | 25–200 μM 24 h |
HeLa HeLa S3 |
___ | c-Jun | Induces autophagosome formation Inhibition of cell proliferation and induction of apoptosis |
[93,94] |
| Rutin | 40–200 μM 24 h |
Caski SiHA |
ROS Bax p53 pRb Casp-2, 8 and 9 p27 |
Hes-1 Notch-1 Bcl-2 CDK4 Cyclin D1 E6 and E7 Jab1 |
Cell cycle arrest at G0/G1 phase Suppression of cell viability Induction of apoptosis |
[97,98,99] |
Abbreviations: Bax (Bcl-2-associated X protein); Casp (caspase); E2F-1 (E2F Transcription Factor 1); IGFBP7 (Insulin Like Growth Factor Binding Protein 7); ROS (Reactive Oxygen Species); STAT3 (Signal transducer and activator of transcription 3); ADAM17 (ADAM Metallopeptidase Domain 17); Atgs (autophagy-related protein); Beclin-1 (B-cell lymphoma 2); c-myc (Myc proto-oncogene); CDK4 (Cyclin-dependent kinase 4); c-Jun (Jun Proto-Oncogene); EGFR (Epidermal growth factor receptor); Hes-1 (hairy and enhancer of split-1); Jab-1 (Jun activation domain-binding protein 1); Mcl-2 (Induced myeloid leukemia cell differentiation protein); NF-KB (nuclear factor kappa-light-chain-enhancer of activated B cells); p-Akt (phosphorylated Akt); PI3K (Phosphoinositide 3-kinases); GSH (glutathione).