Sedanolide

Sedanolide is a natural compound produced in edible umbelliferous plants, such as Celery seed oil [1].

In HepG2 and CaCo-2 cells, treatment with sedanolide (7-500 μM) for 24h showed no effect on cell viability. In HepG2 cells cultured in sedanolide-free medium, sedanolide (500 μM) treatment for 72h decreased cell viability. Pretreatment with sedanolide (100 μM) for 24 h and exposement to either H2O2 or tBOOH did not exhibit statistically significant difference in viability from controls. In HepG2 following 24-h incubation with 500 μM sedanolide, a significant increase in DNA strand breaks was observed. Sedanolide did not modulate H2O2- and tBOOH-induced DNA damage. Sedanolide was relatively nontoxic to cells in culture [1]. Sedanolide (SN) possesses antioxidant effects. In human liver cancer (J5) cells, treatment with sedanolide suppressed J5 cell viability by inducing autophagy. Sedanolide decreased protein expression levels of phosphoinositide 3-kinase (PI3K)-I, mammalian target of rapamycin (mTOR) and Akt and increased PI3K-III, LC3-II and Beclin-1 protein levels. Sedanolide increased the cytosolic phosphorylation of inhibitor of kappa B (IκB) and nuclear p65 and the DNA-binding activity of NF-κB. Sedanolide induced J5 cell autophagy by regulating PI3K, p53 and NF-κB autophagy-associated signaling pathways in J5 cells [2]. Sedanolide (100 μg/ml) inhibited cyclooxygenases-1 and -2 at 250 pg/ml and blocked topoisomerase-I and-II activity [3].

References:
[1] Woods J A, Jewell C, O'Brien N M.  Sedanolide, a natural phthalide from celery seed oil: effect on hydrogen peroxide and tert-butyl hydroperoxide-induced toxicity in HepG2 and CaCo-2 human cell lines[J]. In Vitro & Molecular Toxicology: A Journal of Basic and Applied Research, 2001, 14(3): 233-240.
[2] Hsieh S L, Chen C T, Wang J J, et al.  Sedanolide induces autophagy through the PI3K, p53 and NF-κB signaling pathways in human liver cancer cells[J]. International journal of oncology, 2015, 47(6): 2240-2246
[3] Momin R A, Nair M G.  Antioxidant, cyclooxygenase and topoisomerase inhibitory compounds from Apium graveolens Linn. seeds[J]. Phytomedicine, 2002, 9(4): 312-318.