Abstract:The function of oleanolic acid (OA) in various types of cancer has been reported frequently, especially for breast cancer. However, the regulation of breast tumor growth in response to OA treatment has not been studied in depth. Here, we first explored the effect of OA treatment on breast tumors
in vitro
and
in vivo
and then used RNA-seq technology to study the effect and molecular mechanism of OA treatment of MCF-7 cells, particularly at the level of functional ge… Show more
“…The group of OA treatment showed the smallest tumor volume, suggesting that OA is most effective in inhibiting breast tumor growth in mice. The result is consistent with our previous report [ 21 ]. Fig.…”
“…The group of OA treatment showed the smallest tumor volume, suggesting that OA is most effective in inhibiting breast tumor growth in mice. The result is consistent with our previous report [ 21 ]. Fig.…”
“…The stock solutions were diluted in serum‐free culture medium to a final concentration of 75 µM and filtered using 0.22 µm filters before addition to cells. To stimulate TG accumulation, the HepG2 cells were incubated with 30 mM fructose and 75 µM OLA for 18 h. [ 44 ] Subsequently, HepG2 cells were incubated for 18 h in DMEM with 1% fetal bovine serum (Con), 30 mM fructose and 75 µM OLA (Fru + OLA), or 30 mM fructose and 75 µM OLA, and 200 µM OA (Fru+OLA+OA). Four independent experiments were conducted for each group.…”
Scope
The mechanisms of oleanolic acid (OA) regulating hepatic sterol regulatory element‐binding protein (SREBP) 1c/stearoyl‐CoA desaturase (SCD) 1 pathway to ameliorate fructose‐induced hepatosteatosis are investigated.
Methods and results
Rats treated with 10% w/v fructose solution are co‐administered by OA for 5 weeks, and then sacrifice after fasting for 14 h. OA reverses the fructose‐induced increase in hepatic triglyceride (TG) content and downregulates Scd1 mRNA expression. However, two upstream transcription factors, ChREBP and SREBP1c, remain at normal levels with or without fructose and/or OA. In vivo and in vitro studies using SREBP1c−/− mice and HepG2 cell models show that OA also inhibits SCD1 gene overexpression and high hepatic TG levels induced by fructose. On the other hand, in SCD1−/− mice, when the fructose diet is supplemented with high levels of oleic acid (OLA) to compensate for the deficiency of SCD1, OA inhibits hepatic SREBP1c and lipogenic gene expression and reduces hepatic OLA (C18:1) production to improve fructose and/or OLA induced liver lipid deposition. Furthermore, OA promotes PPARα and AMPK to enhance fatty acid oxidation in fructose + OLA‐fed SCD1−/− mice.
Conclusion
OA may inhibit SCD1 gene expression to ameliorate fructose‐induced hepatosteatosis through SREBP1c‐dependent and ‐independent mechanisms.
“…Recent experiments have reported an antitumor effect of oleanolic acid both in vitro and in vivo, associated with changes in gene expression profile. Screening analyses of MCF-7 cells identified genes related to the p53-, TNF-and mTOR-signaling pathways to be involved in oleanolic acid's antitumoral effects [214]. Moreover, multiple derivates of oleanolic acid have been developed targeting several signaling pathways [215].…”
Breast cancer is the most frequent malignant neoplasia and a leading cause of mortality in women worldwide. The Mediterranean diet has been proposed as a healthy dietary pattern with protective effects in several chronic diseases, including breast cancer. This diet is characterized by the consumption of abundant plant foods and olive oil as the principal source of fat, which is considered one of the main components with potential antioxidant, anti-inflammatory and anticancer effects. Extra-virgin olive oil (EVOO) has several bioactive compounds, mainly including monounsaturated fatty acids, triterpenes and polyphenols, such as phenolic alcohols (e.g., hydroxytyrosol), secoiridoids (e.g., oleuropein and oleocanthal), lignans (e.g., pinoresinol) or flavonoids (e.g., luteolin). While epidemiological evidence is still limited, experimental in vivo and in vitro data have shown a protective effect of this oil and its compounds on mammary carcinogenesis. Such effects account through complex and multiple mechanisms, including changes in epigenetics, transcriptome and protein expression that modulate several signaling pathways. Molecular targets of EVOO compounds have a role in the acquisition of cancer hallmarks. Although further research is needed to elucidate their beneficial effects on human prevention and progression of the disease, evidence points to EVOO in the context of the Mediterranean diet as a heathy choice, while EVOO components may be promising adjuvants in anticancer strategies.
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