Table 1.
Biological test assays and anti-tumor mechanisms of diphyllin as well as its derivatives.
| Compound Number in Original References | Biological Tests and Assays | Anti-Tumor Mechanisms | References |
|---|---|---|---|
| 1, 5, and 7 | MTT | unreported | [9] |
| diphyllin (3) | MTT | unreported | [10] |
| justicidin A (5), diphyllin (3), and tuberculatin (4) | MTT, ELISA kit | tumor necrosis factor-α augment | [11] |
| cleistanone (1), 7 | MTT | unreported | [12] |
| 2-6 | MTT, flow cytometry, P388 leukemia model | G0/G1 phase blockade | [13] |
| 2-5 | MTS | unreported | [14] |
| 1, 3, and 4 | MTT, PI and EB staining, Western blot | mitochondrial-mediated apoptosis induction, Bcl-2 decrease, Bax increase | [15] |
| 5 and 6 | MTT, kDNA decatenation assay, tubulin polymerization assay | Topo II and tubulin inhibition | [16] |
| 3 | MTT, Western blot | Topo II and HADC1 inhibition | [17] |
| 5d | MTT, Western blot | mitochondrial-mediated apoptosis induction, Bcl-2 decrease, Bax increase | [18] |
| 3a and 3e | MTT, colorimetric assay | vacuolar H+-ATPase inhibition | [19] |
| 3a | MTT, colorimetric assay | vacuolar H+-ATPase inhibition | [20] |
| ZT-25 | MTT, Western blot | G1/G0 phase blockade, mitochondrial membrane potential dissipation, ATP depletion, Bcl-2 downregulation, Bax and cleaved caspase-3 upregulation. Autophagy induction, LC3 I to LC3 II, Beclin-1 increase, and p-mTOR decrease | [22] |
| 1e | MTT, lysosome acidity assay | vacuolar H+-ATPase inhibition | [23] |
| 1, 4, and 7 | MTT, transwell invasion assay | unreported | [24] |
| 2I | MTT, vacuolar H+-ATPase activity assay kit | vacuolar H+-ATPase inhibition | [25] |
| diphyllin, 5c3, and 5c4 | MTT, vacuolar H+-ATPase activity assay kit, molecular docking | vacuolar H+-ATPase inhibition | |
| diphyllin | MTT, vacuolar H+-ATPase activity assay kit, Western blot, real-time PCR | Wnt/β-catenin signaling inhibition (phospho-LRP6 and β-catenin expression inhibition, c-Myc and cyclin D1 gene downregulation) | [27] |
| 15 | Sulforhodamine B (SRB), MTT, DNA fragmentation electrophoresis, flow cytometry | topoisomerase II inhibition, G0/G phase arrest | [28] |
| arylnaphthalene lignan (HJC) | MTT, Western blot, real-time PCR | activation of caspase 3 cascade, SOD inhibition, ROS elevation | [47] |
| HJB, HJA, JB, and CME | MTT, SOD activity assay kit, flow cytometry, Western blot | SOD inhibition, ROS elevation, caspase-dependent intrinsic and/or extrinsic apoptosis pathways | [29] |
| 1 and 7 | MTT, Western blot, Topoisomerase II assay, hollow fiber assay | caspase 3-dependent apoptosis | [30] |
| Cleistanthin-A and Cleistanthoside A tetraacetate | MTT, vacuolar H+-ATPase activity assay kit | vacuolar H+-ATPase inhibition | [31] |
| 5 | MTT | unreported | [32] |
| Justicidin B | MTT, Western blot | Bax/Bcl-2 ratio augment and caspase-3/7 activation | [33] |
| Cleistanthin A | MTT, Western blot, vacuolar H+-ATPase activity assay kit | MMP-2 and MMP-9 inhibition, vacuolar H+-ATPase inhibition | [34] |
| diphyllin | MTT, real-time PCR | decreased the mRNA expressions of mTORC1, HIF-1α, and VEGF | [35] |
| 7c | MTT | unreported | [37] |
| M3 | MTT, Western blot, CytoDYNAMIX Screen 03 Tubulin Polymerization assay | caspase 3-dependent apoptosis, promotion of microtubule depolymerization | [36] |
| TAARD | MTT, Western blot | TLR1/NF-κB and TLR3/STAT3 pathway inhibition | [38] |
| Cleistanthin A | MTT, Western blot, real-time PCR | β-catenin pathway inhibition | [39] |
| ECDD-S27 | MTT, immunoblot analysis | restrain of autophagic flux and inhibition of vacuolar H+-ATPase activity | [40] |
| diphyllin derivatives | MTT, UF-LC/MS screening assay, molecular docking | COX-2 inhibition | [41] |
| 15 | MTT, Western blot, flow cytometry, mouse pancreatic cancer model | G0/G1 phase blockade, CDK4, and cyclin D1 decrease | [42] |
| PHY34 | MTT, mass spectrometry-based chemoproteomics | targeting ATP6V0A2 subunit to induce autophagy inhibition and interacting with CAS to alter the nuclear localization of proteins | [44] |
| 3 | MTT, transwell invasion and scratch wound assay, vacuolar H+-ATPase activity assay kit | vacuolar H+-ATPase inhibition | [45] |
| diphyllin | MTT, AO/EB dual staining assay, flow cytometry, wound-healing assay | apoptosis induction | [46] |