br Conclusions ERK and its phosphorylation plays an
Conclusions ERK 1/2 and its phosphorylation plays an essential role in the hippocampus and can be triggered by both ROS accumulation and excessive Ca2+. DBP exposure can also affect the production of ROS and Ca2+ in the hippocampus. The question therefore arises as to whether the cell injury or apoptosis induced by DBP exposure is related to the ERK 1/2 pathway. This is an issue worth exploring. This study has, for the first time revealed that the ERK 1/2 signaling pathway may be a new approach and a new target for drug action in the treatment of related neurodevelopmental disorders induced by DBP. In addition, the combined use of VE and NMDP was shown to ameliorate DBP-induced memory deficit and apoptosis by inhibiting the ERK 1/2 pathway in mice, and provides a reference point for the prevention and treatment of neurotoxicity caused by DBP exposure. The following are the supplementary data related to this article.
Introduction Metastatic melanoma is one of the utmost fatal cancers responsible for 4% of skin cancers and 75% of skin cancer-related deaths (Riker et al., 2010). It presents a serious challenge in clinical medicine, since it is resistant to systemic treatment. Therefore, development of novel therapeutic agents and strategies are urgently needed. Survivin, a member of the inhibitor of apoptosis protein family, is over expressed in tumor CD 2665 molecular to enhance resistance to apoptotic stimuli; hence its over-expression is correlated with recurrence and poor survival (Ejarque et al., 2017). It is expressed in melanocytic nevi and melanoma, but not in normal melanocytes (Ding et al., 2006; Mckenzie and Grossman, 2012; Thomas et al., 2007; Vetter et al., 2005). Increased expression of survivin in UV-induced melanoma exaggerates the development and metastasis of the melanoma cell in HGF-transgenic mice (Thomas et al., 2007). So far, no effective treatment is available for suppression of survivin. However, half-life of survivin protein in post-expression can be regulated by ubiquitin-proteosome pathway. Other studies indicated that phosphorylating modification of survivin via EGF-activated Raf-1/ERK pathway may increase its stability and decrease its proteosome degradation (Wang et al., 2010), thus inhibition of the ERK signaling pathway may effectively suppress survivin expression in melanoma. Hinokitiol may be a good candidate for the inhibition of the ERK signaling pathway. It is a natural tropolone-based monoterpenoid and a component of essential oils first isolated from the heart wood of Chymacyparis taiwanensis. It is a β-thujaplicin with the chemical structure 2-hydroxy-4-isopropylcyclohepta-2,4,6-trien-1-one. It has a variety of pharmacological activities and is an antimicrobial ingredient in food and cosmetic products (Yang et al., 2018). Hinokitiol has no developmental toxicity or carcinogenic effects (Ema et al., 2004; Imai et al., 2006a). Therefore, it has a high degree of safety for potential uses, even at a very high dose (Grillo et al., 2017). Hinokitiol has potential anticancer activity, by disrupting androgen receptor signaling to inhibit the growth of prostate carcinoma cells (Liu and Yamauchi, 2006) or inducing autophagy in breast and colorectal cancer cells (Wang et al., 2016). It exerts anticancer effects through suppressing matrix metalloproteinases (MMPs) and inducing antioxidant enzymes and apoptosis on adenocarcinoma A549 cells (Jayakumar et al., 2018). Melanocytes and melanocyte-derived cells seem to be highly susceptible to hinokitiol. A low dose (5 μM) of hinokitiol inhibits significantly melanogenesis of melanocytes (Choi et al., 2006); and 1–5 μM inhibits invasion capability of melanoma B16-F10 cells via increasing MMP-2 and MMP-9 along with intracellular antioxidant enzymes (Huang et al., 2015a). Although hinokitiol shows promising potential for treatment of melanoma, its therapeutic mechanism is not yet well studied.