The development of chemotherapeutic resistance is a major challenge in oncology. Elevated sphingosine kinase 1 (SK1) levels is predictive of a poor prognosis, and SK1 overexpression may confer resistance to chemotherapeutics. The SK/sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptor (S1PR) signaling pathway has been implicated in the progression of various cancers and in chemotherapeutic drug resistance. Therefore, SK1 may represent an important target for cancer therapy. Targeting the SK/S1P/S1PR signaling pathway may be an effective anticancer therapeutic strategy, particularly in the context of overcoming drug resistance. This review summarizes our current understanding of the role of SK/S1P/S1PR signaling in cancer and development of SK1 inhibitors.
Icariin has been reported to possess high anticancer activity. Colon carcinoma is one of the leading causes of cancer-related mortality worldwide. Here, the anticancer activity of icariin against HCT116 colon carcinoma cells and the possible underlying mechanism were studied. The trypan blue staining assay, wound healing assay, clonogenic assay, CCK-8 assay, and Annexin V-FITC/PI double staining method were carried out to determine the changes of HCT116 cell growth and migration. mRNA and protein expressions were determined by quantitative real-time PCR and western blot, respectively. Moreover, small interfering RNA (siRNA) plasmid was used to examine the role of p53 in icariin-induced apoptosis in HCT116 cells. Icariin significantly suppressed colon carcinoma HCT116 cells by decreasing migration and viability, and simultaneously promoting apoptosis. Icariin exerted the anti-tumor effect in a dose-dependent manner by up-regulating p53. During treatment of icariin, p-p53, p21, and Bax levels increased, and Bcl-2 level decreased. Short time treatment with icariin induced DNA damage in HCT116 cells. Furthermore, the cytotoxicity of icariin was decreased after p53 knockdown or by using caspase inhibitors. p53 was involved in activities of caspase-9 and caspase-3. Icariin repressed colon carcinoma cell line HCT116 by enhancing p53 expression and activating p53 functions possibly through Bcl-2/Bax imbalance and caspase-9 and -3 regulation. Icariin treatment also induced DNA damage in HCT116 cells.
This experiment investigated the effects of supplementing the maternal diet with linseed oil (LSO) and soya bean oil (SBO) on immunoglobulins, the fatty acid composition and hepatic expression of lipid metabolism-related genes in piglets. Multiparous sows (twenty-four per diet) were fed on diets containing a supplement of either SBO or LSO during last week of gestation and lactation. The results indicated that supplementation of maternal diet with LSO could improve the weaning weight of piglets and average daily gain (ADG) (p < 0.05). The concentration of immunoglobulin G (IgG) and immunoglobulin A (IgA) was enhanced in sow plasma, colostrum and milk by the addition of LSO (p < 0.05). In addition, the concentration of 18: 3n-3 fatty acids was higher in the milk of LSO sows. Meanwhile, maternal supplementation with LSO increased the levels of plasma IgG, IgA and the tissues n-3 polyunsaturated fatty acid (PUFA) in piglets (p < 0.05). Correspondingly, the mRNA expression levels of hepatic ∆5-desaturase (D5D) and ∆6-desaturase (D6D) were higher, and fatty acid synthase (FAS) was lower in piglets from LSO-fed sows when compared with that in the SBO group. In conclusion, LSO supplementation of the maternal diet increases immunoglobulins, modifies the fatty acid composition and affects the gene of D5D and D6D expression of piglets.
This study examined the influence of adding different amounts of maternal dietary l‐carnitine and two fat types on fatty acid (FA) composition and the expression of lipid metabolism‐related genes in piglets. The experiment was designed as a 2 × 2 factorial with two fat types (3.5% soyabean oil, SO, and 3.5% fish oil, FO) and two levels of l‐carnitine (0 and 100 mg/kg) added to the sows' diets. A higher proportion of n‐3 polyunsaturated fatty acids (PUFA) and a lower ratio of n‐6/n‐3 PUFA in sow milk and piglet tissues were observed in the FO groups than in the SO groups. Adding l‐carnitine increased the proportion of C16:1 in sow milk and decreased n‐3 PUFA in piglet subcutaneous fat. Hepatic peroxisome proliferator‐activated receptor α (PPAR‐α) was more abundantly expressed in piglets from the FO groups than from the SO groups (p < 0.05), whereas stearoyl‐CoA‐desaturase (SCD), sterol regulatory element binding protein‐1 (SREBP1) and ∆6‐desaturase (D6D) genes were less expressed in the FO groups compared with piglets from the SO groups. The expression of fatty acid synthase (FAS) genes was decreased in the SO groups with l‐carnitine compared to that of the other dietary treatments. No differences among dietary treatments were observed with regard to the expression of acetyl‐CoA carboxylase (ACC). In conclusion, FO and l‐carnitine supplementation in sows affect FA composition and hepatic gene expression in piglets.
The cover image is based on the Original Article l‐carnitine and fat type in the maternal diet during gestation and lactation modify the fatty acid composition and expression of lipid metabolism‐related genes in piglets by Baoming Shi et al., https://doi.org/10.1111/jpn.13099.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.