Fatty Acid Composition of Tissue Cultured Breast Carcinoma and the Effect of Stearoyl-CoA Desaturase 1 Inhibition / 한국유방암학회지

PURPOSE: Stearoyl-CoA desaturase 1 (SCD1) is a novel therapeutic target in various malignancies, including breast cancer. The present study was designed to investigate the effect of the pharmacologic inhibition of SCD1 on fatty acid composition in tissue explant cultures of human breast cancer and to compare these effects with those in adjacent nonneoplastic breast tissue. METHODS: Paired samples of tumor and adjacent noncancerous tissue were isolated from 12 patients with infiltrating ductal breast cancer. Samples were explant cultured in vitro, exposed to the highly selective SCD1 inhibitor CAY10566, and examined for fatty acid composition by gas liquid chromatography. The cytotoxic and antigrowth effects were evaluated by quantification of lactate dehydrogenase release and by sulforhodamine B (SRB) measurement, respectively. RESULTS: Breast cancer tissue samples were found to have higher levels of monounsaturated fatty acids (MUFA) (p<0.001) and arachidonic acid (20:4n-6, p<0.001) and a lower level of linoleic acid (18:2n-6, p=0.02) than the normal-appearing breast tissues. While exhibiting no evident cytotoxicity, treatment with the SCD1 inhibitor, CAY10566 (0.1-1 microM), for 48 hours significantly increased 18:2n-6 levels in both the tumor and adjacent normal-appearing tissue (approximately 1.2 fold, p<0.05). However, the breast cancer tissue samples showed significant increases in the levels of MUFA and 20:4n-6 compared to the normal-appearing breast tissues (p<0.05). The SRB growth assay revealed a higher rate of inhibition with the SCD1 inhibitor in breast cancer tissues than in normal-appearing tissues (p<0.01, 41% vs. 29%). The SCD1 inhibitor also elevated saturated fatty acid (1.46-fold, p=0.001) levels only in the tumor tissue explant. CONCLUSION: The fatty acid composition and response to SCD1 inhibition differed between the explant cultures from breast cancer and the adjacent normal-appearing tissue. Altered fatty acid composition induced by SCD1 inhibition may also, in addition to Delta9 desaturation, modulate other reactions in de novo fatty acid synthesis and lipogenesis, and subsequently affect the overall survival and progression of breast cancer.

Correlation between PPAR gamma protein expression level in granulosa cells and pregnancy rate in IVF program

Peroxisome proliferative-activated receptors [PPARs] are nuclear receptors that involved in cellular lipid metabolism and differentiation. The subtype gamma of the PPAR family [PPAR gamma] plays important roles in physiologic functions of ovaries. To determine correlation between PPAR gamma protein level in granulosa cells and pregnancy rate in women undergoing in-vitro fertilization [IVF] treatment. In this cross-sectional study, twenty-five samples of granulosa cells were collected from women referred to an IVF treatment center. PPAR gamma protein expression level in granulosa cells was determined in comparison with beta -actin level as control gene with Western blot test. Laboratory pregnancy was determined by a rise in blood beta -hCG level fourteen days after embryo transfer. Correlation analyses were used to test for associations between the oocytes and pregnancy occurrence as outcome variables and PPAR gamma protein expression level. Correlation analysis indicated that there was no significant relationship between granulosa cells PPAR gamma protein level with IVF parameters including number of matured oocytes and the ratio of fertilized to matured oocytes. Comparison of granulosa cells PPAR gamma protein level with positive and negative laboratory pregnancy revealed also no significant relationship. According to the results of this study, PPAR gamma protein level in granulosa cells could not be directly correlated to the success rate of IVF

Fatty acid composition of human follicular fluid phospholipids and fertilization rate in assisted reproductive techniques

Fatty acids are known to be critically important in multiple biological functions. Phospholipid fatty acids of follicular fluid, an important microenvironment for the development of oocytes, may contribute to the women's fertility and the efficacy of assisted reproduction techniques. The aim of this study was to investigate the effect of fatty acid composition of follicular fluid phospholipids on women undergoing assisted reproductive techniques. Follicular fluid samples were obtained from 100 patients, referred to Tabriz Alzahra Hospital. Seventy-nine subjects underwent in vitro fertilization [IVF] and the remaining 21 underwent intracytoplasmic sperm injection [ICSI]. Total lipid of follicular fluid was extracted and fatty acids were analyzed by gas-liquid chromatography. Saturated fatty acids [SFA, P = 0.002] and the ratio of SFA to polyunsaturated fatty acids [P = 0.001] were correlated negatively with a number of mature oocytes after age adjustment. Linoleic acid [P = 0.006] was positively correlated, while the level of arachidonic acid was negatively correlated with fertility percentage after adjustment for body mass index, sperm count, sperm motility. Since phospholipids are one of the major components of lipid metabolism, the results of this study highlight the importance of this component in follicular fluid lipid metabolism. Consequently, it is proposed as an index in determination of the rate of success in assisted reproductive techniques such as IVF/ICSI

Correlation between the level of cholesteryl ester transfer protein in follicular fluid with fertilization rates in IVF/ ICSI cycles

Follicular fluid [FF] plays an important role in oocytes and embryo development, which may contribute to IVF/ICSI success rate. The aim of this study was to investigate the correlation between cholesteryl ester transfer protein [CETP] level in FF and the success rate of IVF/ICSI. In a cross-sectional study, FF samples, FF samples were obtained from 100 patients referred to Tabriz Alzahra Hospital. Seventy-nine subjects underwent IVF and the remaining 21 underwent ICSI. The levels of high-density lipoprotein cholesterol [HDL-C], apolipoprotein A-I and CETP were measured using enzymatic, turbidometric and ELISA methods respectively. Analysis of the subgroups with different levels of CETP showed a significant lower level of CETP in the subgroup with the lowest number of mature oocytes [p<0.05]. The level of CETP was also considerably lower [18%, p=0.05] in subjects with<50% oocytes fertilization ratio than subjects with >70% of this ratio. While no association was found for pregnancy, the amount of CETP in FF was associated positively to the maturity and the percentage of oocyte fertilization