erastin is a ferropoptosis inducer that is currently under evaluation as an anti - cancer treatment. in ovarian carcinoma hey cells, 100 μm ole was not able to affect cell viability, but acted as an antioxidant, decreasing endogenous and erastin - dependent lip and ros levels, preventing erastin - dependent ros accumulation in mytochondria and increasing glutathione peroxidase 4 ( gpx4 ) levels that were reduced by erastin treatment, finally counteracting erastin - induced cell death. it remains to be demonstrated if nu trit ionally relevant and / or non - cytotoxic concentrations of ole and ht may offer a survival advantage to neoplastic cells. a similar scenario has been described for other antioxidants ( e. g., n - acetyl - l - cysteine, alpha - tocopherol and carotenoids ), which showed a pro - tumorigenic action by exerting beneficial effects on cancer cells. it will be fundamental to deepen these pieces of data in order to rule out the chance that ole and ht may promote cancer growth and metastasis. another risk factor for tumorigenesis is inflammation. ros imbalance itself may drive inflammation, inducing the production of pro - inflammatory cytokines interleukin-1 ( il - 1 ), il - 6, il - 8, and tumor necrosis factor - α ( tnf - α ). persisting ( chronic ) or poorly controlled inflammation may directly promote tumorigenesis due to the action of ros and the recruitment of immune cells triggering the release of growth signals and the activation of tissue repair mechanisms. after cancer insurgence, the production of inflammatory mediators sustained by cancer cells and surrounding actors ( tissue macrophages, cancer - associated fibroblast, infiltrating immune cells, and endothelial cells, among the others ) contributes to the creation of an environment favoring immune evasion, cell survival, invasion, and angiogenesis. chemotherap y may also account for an exacerbation of inflammation, whose biological meaning is poorly understood, being recognized as immune - activating as well as a contributor to the failure of the therapeutic regimen. ole and ht exhibit an anti-inflammatory activity that has been demonstrated in multiple in vivo and in vitro models, although some experimental variables related to the timing of administration of inflammatory stimuli might have affected the reproducibility of the results, mainly in vitro, and nu trit ionally relevant concentrations of ole and ht often showed no anti-inflammatory activity on human peripheral blood mononuclear cells. proof of ole and ht modulation of inflammation in cancer cells has been obtained mostly from colorectal cancer. in an in vivo model of aom / dss - induced colorectal cancer in c57bl / 6 mice, 50 mg / kg and 100 mg / kg ole reduced il - 6, tnf - α, and ifn - γ colon tissue levels, as well as cox - 2 levels. treatment of hct116 and lovo cells with 0. 0154 mg / ml ( ≈100 μm ) ht and 0. 0231 mg / ml ( ≈150 μm ) ht, respectively, for 72 h reduced phosphorylation of nf - κb p65, in turn leading to a reduction in pro - inflammatory cytokines tnf - α and il - 8 at both mrna and protein levels. ht - dependent anti-inflammatory effect was also mediated by ht - elicited increase in protein levels of pparγ. in addition, ht acted as a pparγ agonist, promoting its transcriptional activity. in ht - 29 cell line, 100 – 400 μm reduced tnf - α - induced nf - κb activation in a dose - dependent manner. in in vitro models, the frame appears completely different. the only ht concentrations that elicited a reduction in il - 6 levels were 80 μm for hepg2 and 30 μm for hep3b. ht doses of 100 μm and 200 μm in hepg2 and 80 μm, 100 μm, and 200 μm in hep3b cells produced an increase in il - 6 release. treatment of k562 cells with 100 μm ht produced transcriptional effects including the downregulation of il - 10 receptor and the upregulation of inflammatory mediators il - 6 and il - 8. ole and ht may participate in control of cancer - associated and chemotherap y - dependent tissue inflammation by acting on non - tumor cells. as demonstrated in vivo, treatment of balb / cn mice with 5, 10, and 20 mg / kg ole suppressed signs of cisplatin - induced renal inflammation, including tissue modulation of tnf - α levels. four cycles of 150 mg / kg / week ole in sprague – dawley rats reduced serum tnf - α and il - 6 in an experimental model of epirubicin and cyclophosphamide toxicity. in a model of cyclophosphamide - induced immunosupp ression in broilers, a solution containing 200 mg / l ht promoted the duodenal expression of anti-inflammatory cytokines il - 4 and il - 10. it remains to be assessed if such a modulatory activity is able to contribute to the immunosuppressant environment surrounding cancer cells. from the analysis of the literature reported in this review, it becomes evident that the multifaceted nature of ole and ht interaction with molecular mediators in cancer cells and non - cancer tissues determines the need for safe strategies to improve ole and ht bioavailability and delivery, also offering a more stable and highly selective anti - proliferative activity throughout time. different approaches have been evaluated to reach this objective through the development of ole and ht derivatives or carrier systems. for example, peracetylated ole had a stronger anti - proliferative and antioxidant activity than ole in thyroid and breast cancer in vitro; iron oxide nanoparticles coated with glucose and conjugated with ole showed a notable cytotoxic action against colorectal cancer cell line sw480; chitosan nanoencapsulation of ht was shown to be unaffected by time - dependent dynamic changes in efficacy observed for free ht in lung and breast cancer cell lines; hydroxytyrosyl dodecyl ether, an ht alkyl ether derivative, had a very strong cytotoxic activity at low concentrations ( ic50 = 19. 9 ± 4. 6 μm ) in lung cancer cells in vitro; hydroxytyrosyl oleate, an ht ester, exerted the same effects shown by ht on sh - sy5y neuroblastoma cells at lower concentrations; ht - loaded poly lactide - co - glyco lide - co - polyacr ylic acidnanoparticles exhibited cytotoxic and transcriptional regulating effects at lower concentrations ( 6 ppm ) than free ht in colorectal cancer in vitro. anyway, it would be highly recommendable to address future ole - and ht - specific research directions towards the exploration of the true effect of nu trit ionally relevant concentrations of these phenols ( or ole and ht concentrations that can realistically be maintained in plasma ) on cancer cells, since even most recent evidence is not able to determine if the administration of ole and ht in humans could be detrimental in terms of tumor growth and anti - cancer drug metabolism / effects. up to now, conclusive studies assessing the influence of nu trit ionally relevant concentrations of ole and ht on tumor insurgence and expansion, as well as proof of the absence of ole - and ht - mediated alterations of chemotherap y metabolism, are still missing. another important reason for concern is represented by ole and ht context - dependent dual action as both antioxidant and pro - oxidant agents, since such a behavior may alter the efficacy of cancer treatment in unexplored ways. also, ole and ht modulatory activity on immune cells deserves further investigation. currently, neither ole nor ht could be safely considered as cancer - preventive agents or drugs for combinatory therapies without excluding the possibility that nu trit ionally relevant concentrations of these compounds might facilitate neoplastic cell expansion or even treatment escape. backgroundhuman stem cells are viewed as a possible source of neurons for a cell - based therapy of neurodegenerative disor ders, such as parkinson ' s disease. several protocols that generate different types of neurons from human stem cells ( hscs ) have been developed.