TABLE 2.
Substances that have an inhibitory effect on tumors by mediating necroptosis.
| Classification | Name | Source | Mechanism |
|---|---|---|---|
| Natural compounds or extracts | 2-methoxy-6-acetyl-7methyljuglone (MAM) (Sun et al., 2016; Sun et al., 2019b) | A naphthoquinone isolated from polygonum cuspidatum | Induce NO-dependent necroptosis or apoptosis mediated by H2O2-dependent JNK activation in cancer cells |
| Tanshinol A (TSA) (Liu et al., 2020a) | A tanshinone that isolated from the roots of Danshen | Trigger MLKL-dependent necroptosis that independent RIPK1/RIPK3 and calcium. ROS might promote the upstream of MLKL. | |
| sea hare hydrolysates (SHH) (Nyiramana et al., 2020) | A hydrolysate from Sea Hare | SHH has effects against lung cancer by activating M1 (as anti-tumor effects), reducing M2, inhibiting growth and migration, and being cytotoxicity. Pyroptosis/necroptosis take part in SHH-induced anticancer effects under STAT3 inhibition | |
| Shikonin (Kim et al., 2017) | Purified from lithospermum erythrorhizon | Induce necroptosis and autophagy in NSCLC cells. Necroptosis is enhanced by inhibition of shikonin-induced autophagy | |
| Citronellol (Yu et al., 2019) | A monoterpene having the molecular formula of C10H20O | Induce necroptosis of NCI-H1299 cells by TNF- α pathway and ROS accumulation | |
| Substances in tumor cells | Betanodavirus B2 protein (Chiu et al., 2017) | Encoded by a sub-genomic RNA3 in betanodaviruses replication | Trigger apoptosis required P53 activation and RIPK3-dependent necroptosis by ROS |
| Sirtuin (SIRT3) (Tang et al., 2020) | A member of the Sirtuin family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases | Keep mutant p53 stable by controlling proteasomal degradation triggered by ubiquitylation and has anti-tumor effects by inducing apoptosis and necroptosis | |
| Kras-derived exosomes (Petanidis et al., 2020) | A exosomes | Treatment with carboplatin and inhibition of Kras secreted exosomes induce TNFα-mediated RIPK3-dependent necroptosis and reduce miR-146/miR-210 levels that have the effects of immunosuppressive. Reduction in miR-146/miR-210 levels accompanied by a reduction in immunosuppressive | |
| PITPα(Jing et al., 2018) | A family member of PITPs | Promote cisplatin-induced MLKL-dependent necroptosis by increasing oligomerization and plasma membrane translocation | |
| Synthetic compound | 3-bromomethylbenzofuran-2-carbox-ylic acid ethyl ester (MCC1019) (Abdelfatah et al., 2019) | Drug-like compounds | Suppress AKT signaling pathway activation. prolong mitotic arrest and induced apoptosis and necroptosis |
| 2-amino-2-[2-(4-octylphenyl)ethyl] propane-1,3-diol; Fingolimod, Novartis ( FTY720) (Saddoughi et al., 2013) | A synthetic sphingosine analogue of myriocin | Binds I2PP2A/SET then activate PP2A tumor suppressor signaling, and induce RIPK1-mediated necroptosis | |
| LGH00168 (Ma et al., 2016) | Drug-like compounds, C/EBP homologous protein (CHOP) activator | A CHOP activator that induces necroptosis by ROS-mediated ER stress, CHOP activation, and NF-kB inhibition | |
| ethyl 6-(5-(phenylsulfonamido)pyridin-3y-l)imidazo [1,2a]pyridine-3-carboxylate (HS-173) (Park et al., 2019) | The imidazopyridine derivative | Induce necroptosis by enhancing RIPK3 expression and activating the RIPK3/MLKL signaling pathway in lung cancer cells | |
| PK68(Hou et al., 2019) | A potent and selective type II RIPK1 inhibitor | Prophylactic use of PK68 has an inhibitory effect on tumor metastasis |