Table 3.
Natural terpenoids targeting HDAC in human cancers.
| Molecules (Origins) | Used Models | Methods | Key Findings | Ref. |
|---|---|---|---|---|
| Corosolic acid (Purchased) | TRAMP-C1 cells | RT-PCR DNA extraction HDAC activity assessment ChIP assay Western blot analysis |
Increased the acetylation of histone H3 lysine 27 (H3K27ac). Reduced trimethylation of histone H3 lysine 27 (H3K27Me3) in the Nrf2 promoter region. Reduced the expression and activity of epigenetically modifying enzymes in TRAMP-C1 cells. |
[232] |
| Cucurbitacin B (L. graveolense Roxb.) | NSCLC cells | RT-PCR Western blot analysis HDAC activity Immunohistochemical staining |
Altered histone modifications. | [233] |
| Parthenolide (PTL) (Purchased) | ZR-75-1 and 293T cells | RT-PCR HDAC activity Western blot analysis ChIP assay |
Depleted HDAC1 protein, without affecting Class I/II HDAC proteins. HDAC1 depletion and cell death were promoted by the mutant DNA-damage transducer ataxia telangiectasia. |
[236] |
| Parthenolide (PTL) (Purchased) | AML cells | Methylcellulose colony-forming Western blot analysis Flow cytometry |
HDAC induced apoptosis was prevented in multiple human AML cells. Increased HDAC-induced lethality. PTL + HDACis caused apoptosis in MLL-ENL cells. PTL + HDACis triggered SAPK/JNK activation. |
[237] |
| Parthenolide (PTL) (Not reported) | JB6 cells | Western blot analysis ChIP method RT-PCR siRNA transfection HDAC activity |
Modulated gene expression. | [238] |
| Parthenolide (PTL) (Purchased) | MDA-MB231 cell line | Cell viability assessment ROS and GSH analysis Western blot analysis |
PTL + HDACi induced GSH depletion, Cyt c release, activation of caspase 3 and apoptosis. PTL + HDACi sustained both HDACi-induced hyperacetylation of histones H3 and H4 and PTL-induced downregulation of DNMT1 expression PTL + HDACi boosted PTL’s cytotoxic impact. |
[239] |
| Ursolic acid (Purchased) | JB6 P+ cells | qPCR Western blot analysis HDAC activity assay |
Reduced the expression of HDAC1, 2, 3, and 8 (Class I) enzymes and the activity of HDAC6 and 7 (Class II). | [240] |
| Ursolic acid (Purchased) | Male Sprague-Dawley rats | mRNA expression measurement qPCR Development of PK/PD model |
Inhibited the induction of epigenetic markers in leukocytes. | [232] |
| Z-Ligustilide (LIG) (Purchased) | HS578t, MDA-MB-231 and MDA-MB-453 cells | Western blot analysis Luciferase assay ChIP assay Immunoprecipitation |
Increased Ace-H3 (lys9/14) enrichment in the ER promoter. Downregulated the HDAC activity. |
[241] |