TABLE 1.
Involved cancer-related signaling pathways in PTOX derivatives treatment.
| PTOX derivatives | Cancer type | Potential downstream targets | Therapeutic remarks | References |
| 4β-amidopodophyllotoxins | Breast cancer | p53, cyclin B1, Cdk1, VEGF-A, STAT-3, ERK1/2, ERK-p, AKT-1, etc. | Induced cell cycle arrest | Kamal et al., 2013 |
| XWL-1–48 | Breast cancer | PI3K/AKT/Mdm2 | Induced cell cycle arrest and cell apoptosis | Wang Y. et al., 2018 |
| PTOX | Breast cancer | P53/PLK1 | Inhibited cell proliferation, migration, and invasion; Induced cell cycle arrest and cell apoptosis | Zhang et al., 2020 |
| PTOX-norcantharidin hybrids | Breast cancer | CDK1 and cyclin B1 | Induced cell cycle arrest, microtubules depolymerization, and cell apoptosis | Han et al., 2016 |
| PTOX | Lung cancer | c-MET kinase, cyclin B1, cdc2, and p27 | Induced cell apoptosis | Oh et al., 2021 |
| Ching001 | Lung cancer | ER stress signaling pathway | Induced microtubules depolymerization | Chen et al., 2013 |
| β-apopicropodophyllin | Lung cancer | ER stress signaling pathway and caspases | Induced microtubules depolymerization and cell apoptosis | Kim et al., 2018 |
| 4β-cinnamic acid-linked PTOX | Lung cancer | PARP, caspase-3, Bax, and Bcl-2 | Induced cell cycle arrest and cell apoptosis | Kamal et al., 2015 |
| Deoxypodophyllotoxin derivatives | Lung cancer | p53/cdc2/Bax/Bcl-2 and caspase-3 | Induced cell cycle arrest | Sang et al., 2013 |
| PTOX acetate | Lung cancer | ER stress pathways; caspase−3, −8 and, −9; beclin-1, Atg3, Atg5, Atg7, and LC3 | Induced cell cycle arrest, cell apoptosis, autophagy | Choi et al., 2015b; Hong et al., 2016 |
| HY-1 | Colorectal cancer | Cdc2, Chk1, Chk2, and ATR | Induced cell cycle arrest and cell apoptosis | Zhao et al., 2013 |
| 4DPG | Colorectal cancer | Chk2/Twist1/EMT | Attenuated EMT-related proteins expression | Katoch et al., 2021 |
| XWL-1–48 | Hepatocellular carcinoma | cyclinA/Cdk2 complex; Bax/Bcl2 | Induced cell cycle arrest and cell apoptosis | Wang et al., 2017 |
| DPODO | Hepatocellular carcinoma | IL-6, NF-κB, TGF-β, and α-SMA | Lowered the inflammatory and fibrogenic factors in the liver | Sharma et al., 2019 |
| MPTOX | Bladder cancer | TUBB3 and TOPIIA | Induced cell apoptosis | Sadeghi et al., 2015 |
| PTOX-indirubin hybrids | Leukemia | CDK1, CDK2, JNK, AKT, Beclin1, and LC3-II | Induced cell cycle arrest, cell apoptosis, and autophagy | Wang J. et al., 2018 |
| L1EPO | K562/A02 and KBv200 | mdr-1 | Anti-MDR | Chen et al., 2009 |
| YB-1EPN | KBV200 and K562/A02 | mdr-1 and bcl-2 | Anti-MDR | Chen et al., 2010 |
| 4β-anilino-PTOX | KB/VCR | mdr-1 | Anti-MDR | Hu et al., 2010 |
| Pyridine acid esters of PTOX | K562/ADR | ERK1/2 | Anti-MDR | Zhang et al., 2016a |
| Aromatic heterocyclic esters of PTOX | K562/ADR | ROS/MAPK | Anti-MDR | Zhang et al., 2016b |
| PtoxPdp | Hepatocellular carcinoma | PI3K/AKT/mTOR and NF-κB/Snail | Attenuated EMT-related proteins expression | Li et al., 2019b |
| PtoxDpt | Hepatocellular carcinoma | p53/PI3K/AKT/mTOR/EMT | Attenuated EMT-related proteins expression | Li et al., 2019c |
| SU212 | Breast cancer | AMPK/HIF-1α | Regulate the Warburg effect | Tailor et al., 2021 |