Sedanolide induces autophagy through the PI3K, p53 and NF-κB signaling pathways in human liver cancer cells

Abstract

Abstract. Sedanolide (SN), a phthalide-like compound from celery seed oil, possesses antioxidant effects. However, the effect of SN on cell death in human liver cancer cells has yet to be determined. In this study, cell viability determination, monodansylcadaverine (MDC) fluorescent staining and immunoblot analysis were performed to determine autophagy induction and autophagy-induced protein expression changes via molecular examination after human liver cancer (J5) cells were treated with SN. Our studies demonstrate that SN suppressed J5 cell viability by inducing autophagy. Phosphoinositide 3-kinase (PI3K)-I, mammalian target of rapamycin (mTOR) and Akt protein levels decreased, whereas PI3K-III, LC3-II and Beclin-1 protein levels increased following SN treatment in J5 cells. In addition, SN treatment upregulated nuclear p53 and damage-regulated autophagy modulator (DRAM) and downregulated cytosolic p53 and Tp53-induced glycolysis and apoptosis regulator (TIGAR) expression in J5 cells. Furthermore, the cytosolic phosphorylation of inhibitor of kappa B (IκB) and nuclear p65 and the DNA-binding activity of NF-κB increased after SN treatment.These results suggest that SN induces J5 cell autophagy by regulating PI3K, p53 and NF-κB autophagy-associated signaling pathways in J5 cells. IntroductionHuman hepatocellular carcinoma (HCC) is one of the most common malignant tumors and a significant cause of mortality in several regions of Africa and Asia (1,2). Triggering cancer cell death to reduce cancer cell number and inhibiting cancer cell proliferation by phytochemicals or chemotherapeutic agents represent some of the most effective current anticancer strategies (3). Cell death can occur through one of three pathways: necrosis, apoptosis or autophagy (4).Autophagy is induced by various physiological conditions, such as mitochondrial damage, protein aggregation, pathogen infection and nutrient starvation (5,6). Autophagy is a multi-step cellular pathophysiological program, including initiation (pre-autophagosome formation), autophagosome formation, maturation and degradation (7). In these steps, phosphoinositide 3-kinases (PI3Ks) play key regulatory roles in many cellular processes, including cell survival, proliferation and differentiation (8-10). Both class I PI3K (PI3K-I)/Akt/ mammalian target of rapamycin (mTOR) and Beclin-1/class III PI3K (PI3K-III)/LC3-II signaling pathways are involved in pre-autophagosome formation (11-14). Cytosolic and nuclear p53, damage-regulated autophagy modulator (DRAM) and the p53-induced glycolysis and apoptosis regulator (TIGAR) are involved in autophagosome formation (15). In addition, p53 initiates a cascade of starvation signals and triggers a starvation-like response by inhibiting mTOR (16). Furthermore, p53 activates both the DRAM and PI3K-III pathways upon autophagosome formation (15). Phytochemicals or chemical agents that regulate p53-and PI3K-mediated autophagy induction could serve as a potential starting point for novel methods of cancer prevention and treatment.The transc...

Ultrasound-Assisted Hydrodistillation of Essential Oil from Celery Seeds (Apium graveolens L.) and Its Biological and Aroma Profiles

“…According to the literature, celery seed contains approximately 2% of volatile oil [9]. Previous literature studies do not show this method of treatment in the case of hydrodistillation of essential oil from celery seeds.…”

“…The volatile constituents having a phthalide skeleton: sedanenolide, 3-butylphthalide, sedanolide, and Z-ligustilide are responsible for the celery-like aroma of the essential oil and the whole plant [6,9]. The first two of these were identified in the essential oil from sonicated celery seeds.…”

Tanshinone I induces cell apoptosis by reactive oxygen species-mediated endoplasmic reticulum stress and by suppressing p53/DRAM-mediated autophagy in human hepatocellular carcinoma

“…Additionally, Cui et al reported that p53/DRAM-mediated autophagy contributes to radiation-induced death in MCF-7 breast cancer cells [38]. Hsieh et al reported that sedanolide promotes autophagy via the p53/DRAM signaling pathway in human liver cancer J5 cells [39]. Wei et al also demonstrated that XingNaoJing inhibits autophagy by suppressing the p53/ DRAM signaling pathway in PC12 cells [12].…”

NF-κB-Mediated Inflammation in the Pathogenesis of Intracranial Aneurysm and Subarachnoid Hemorrhage. Does Autophagy Play a Role?

“…RelA(p65), a member of the NF-κB family, can target several sites in the promoter of the BECN1 ( Beclin 1 ) gene, modulating the level of autophagy in various human cell lines [ 58 , 59 ]. In turn, other members of the NF-κB family can be activated by DNA damage with the involvement of autophagy, as reported for many cell lines and several signaling proteins [ 60 , 61 , 62 , 63 , 64 , 65 ]. Bcl-2/E1B-19K interacting protein 3 (BNIP3) is a mitochondrial protein cooperating with several anti-apoptotic proteins and inducing cell death with the involvement of autophagy [ 66 , 67 ].…”