It has been suggested that the estrogen receptor alpha (ERα) and vitamin D receptor (VDR) genes as possibly implicated in reduced bone mineral density (BMD) in osteoporosis. The present study investigated the relation of ERα PvuII/XbaI polymorphisms and VDR FokI/TaqI polymorphisms with BMD in Turkish postmenopausal women. Eighty-one osteoporotic and 122 osteopenic postmenopausal women were recruited. For detection of the polymorphisms, polymerase chain reaction-restriction fragment lenght polymorphism techniques have been used. BMD was measured at the lumbar spine and hip by dual-energy X-ray absorptiometry. Distributions of ERα (PvuII dbSNP: rs2234693, XbaI dbSNP: rs9340799) and VDR genotypes (FokI dbSNP rs10735810, TaqI dbSNP: rs731236) were similar in study population. Although overall prevalence of osteoporosis had no association with these genotypes, the prevalence of decreased femoral neck BMD values were higher in the subjects with ERα PvuII "PP" and ERα XbaI "XX" genotypes than in those with "Pp/pp" genotypes and "xx" genotype, respectively (P < 0.05). Furthermore, subjects with VDR FokI "FF" genotype had lower BMD values of femoral neck and total hip compared to those with "Ff" genotype (P < 0.05). In the logistic regression analysis, we confirmed the presence of relationships between the VDR FokI "FF" genotypes, BMI ≤ 27.5, age ≥ 55 and the increased risk of femoral neck BMD below 0.8 value in postmenopausal women. The present data suggests that the ERα PvuII/XbaI and VDR FokI polymorphisms may contribute to the determination of bone mineral density in Turkish postmenopausal women.

Researchers have started focusing on investigating the anticarcinogenic effects of natural products with the slightest side effects possible, because current breast cancer treatment approaches are unable to achieve absolute success especially on aggressive subtypes. Propolis is among these products with its antimicrobial, antifungal, anti‐inflammatory, and anticancer effects. Therefore, seven different samples were collected from different regions (Argentina, China, and Istanbul‐Turkey) and applied on nonaggressive breast cancer cell line (BCCL) MCF‐7 and aggressive cell lines SK‐BR‐3, and MDA‐MB‐231. Initially, the phenolic/flavonoid constituents of the propolis ethanol extracts were investigated by liquid chromatography‐mass spectrometry–mass spectrometry (LS‐MS/MS) and high‐performance liquid chromatography (HPLC) analyses. Then, the anticarcinogenic effects of the propolis samples on MCF‐7, SK‐BR‐3, MDA‐MB‐231 were evaluated by WST1 analysis and only selected ones on MCF‐10A and hPdLF. According to the LS‐MS/MS and HPLC analysis, Turkey originated propolis (Turkey3) were found to be richer than the other propolis samples in terms of phenolic/flavonoid compounds. Turkey propolis significantly inhibited cell proliferation in both nonaggressive and aggressive BCCL (P < 0.01). Therefore, Turkey3 propolis was selected for further evaluation using Annexin V‐PI apoptosis detection assays. In addition, selected compounds among the propolis contents such as galangin, caffeic acid, apigenin, quercetin, and ferulic acid were applied to the MCF‐7 cell line to detect cytotoxic and apoptotic effects. Galangin, caffeic acid, apigenin, and quercetin remarkably induced cell proliferation inhibition at all time intervals, whereas ferulic acid was found non efficient on the MCF‐7 cell line. Annexin V‐PI assay clarified that all cell proliferation inhibitions were markedly apoptotic. Our findings indicated that the inhibition effect of propolis on breast cancer cell proliferation was in a propolis type‐, dose‐ and time‐dependent fashion. Turkey3 propolis showed statistically significant cytotoxic effects on both the nonaggressive and aggressive BCCL. These findings were consistent with the effects of its rich phenolic and flavonoid contents, in terms of variety. © 2018 IUBMB Life, 71(5):619–631, 2019

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Natural products with bioactive components are widely studied on various cancer cell lines for their possible cytotoxic effects, recently. Among these products, honey stands out as a valuable bee product containing many active phenolic compounds and flavonoids. Numerous types of multifloral honey and honeydew honey are produced in Turkey owing to its abundant vegetation. Therefore, in this study, we investigated the cytotoxic effects of particular tree-originated honeys from chestnut, cedar, pine, and multifloral honey on cell lines representing different types of the most common cancer of women, breast cancer, MCF7, SKBR3, and MDAMB-231, and fibrocystic breast epithelial cell line, MCF10A as a control. All honey samples were analyzed biochemically. The dose- (1, 2.5, 5, 7.5, and 10 µg/mL) and time (24th, 48th, and 72nd hours)-dependent effects of ethanol/water solutions of the honey samples were scrutinized. Cell viability/cytotoxicity was evaluated by the water soluble tetrazolium Salt-1 (WST-1) method. Apoptotic status was detected by Annexin V-PI assay using FACSCalibur. The statistical analysis was performed using GraphPad Prism 6 and the clustering data analysis with the R programming language. The biochemical analyses of the honey samples showed that the tree-originated honey samples contained more total phenolic compounds than the multifloral honey. Phenolic content of the honey types increases in order of multifloral, pine, cedar, and chestnut, respectively, which is compatible with their cytotoxic affectivity and dark color. In addition, the antioxidant capacity of the studied honey types was observed to increase in order of multifloral < pine < cedar ≅ chestnut. According to the WST-1 data, chestnut honey induced cytotoxicity over 50% on all the cell lines, including the control MCF10A cells, even with low doses (honey concentrations starting from 1 µg/mL) (P < 0.0001). Similarly, Cedar honey was observed to be the second most effective honey in this study. Cedar honey, with the dose of 1 µg/mL, was detected statistically highly significant on MCF10A, MCF7, and SKBR3. In contrast, pine honey showed dramatically significant cytotoxicity only on the MDAMB 231 cells with a 1 µg/mL dose at the same time point (P = 0.018). While pine honey caused an anticancer effect on the MCF-7 and SKBR3 cancer cell lines with a 2.5-5 µg/mL dose (P < 0.0001), like cedar and chestnut honeys, it increased the viability of the MCF10A control cells with the doses of 2.5-5 µg/mL. It only showed cytotoxicity with higher doses (10 µg/mL) on the MCF10A cell line (P < 0.0001). Moreover, we have observed that the multifloral and artificial honey samples were mostly ineffective or increased cell viability with the doses of 1-5 µg/mL. Apoptotic effects of the other honey samples on the MCF-7 cell line were found as chestnut> pine> cedar> multifloral in the Annexin V-propidium iodide (PI) analysis. Chestnut, cedar, and pine honey displayed a remarkably cytotoxic effect on breast cancer cell lines, MCF7, SKBR3, and even on the most agg...

Although HER2/PTEN pathway is commonly disrupted in cancer, association of HER2 and PTEN polymorphisms with breast cancer (BC) remains controversial. We investigated the HER2 Ile655 Val and PTEN IVS4 polymorphisms in patients with BC in Turkish population. HER2 Ile655Val (rs 1136201) and PTEN IVS4 (rs 3830675) polymorphisms were determined using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) in blood samples of 118 BC patients and 118 age-matched healthy controls. We found that the frequency of the Ile/Val genotype of HER2 Ile655Val gene was significantly higher in BC patients (p < 0.009; OR: 1,983 95 % CI: 1.181-3.328). The presence of ATCTT insertion (+/+) genotype at downstream of exon 4 in intron 4 of PTEN IVS4 gene was also associated with 1.83 fold decreased risk of BC development (p < 0.033; OR: 1.83, 95 % CI: 1.11-3.03). Analysis on clinico-pathological parameters showed neither HER2 Ile655Val nor PTEN IVS4 genotypes were not associated with any of the variables (p > 0.05).In conclusion, our findings suggest that the Ile/Val genotype of HER2 and ATCTT insertion (+/+) genotype of PTEN IVS4 gene may play an important role as genetic markers for breast cancer risk, but both genes genotypes may not be useful for predicting tumor prognosis in Turkish population.