Drug resistance is a well-known and significant obstacle in the battle against cancer, rendering chemotherapy treatments often ineffective. To improve the effectiveness of chemotherapy, researchers are exploring the use of natural molecules that can enhance its ability to kill cancer cells and limit their spread. Docosahexaenoic acid (DHA), a lipid found in marine fish, has been shown to enhance the cytotoxicity of various anti-cancer drugs in vitro and in vivo. While the combined use of chemotherapeutic drugs with DHA demonstrated promising preliminary results in clinical trials, there is still a significant amount of information to be discovered regarding the precise mechanism of action of DHA. As the biological pathways involved in the chemosensitization of already chemoresistant MCF-7 cells are still not entirely unraveled, in this study, we aimed to investigate whether DHA co-treatment could enhance the ability of the chemotherapy drug doxorubicin to inhibit the growth and invasion of MCF-7 breast cancer cells (MCF-7/Dox) that had become resistant to the drug. Upon treating MCF-7/Dox cells with DHA or DHA–doxorubicin, it was observed that the DHA–doxorubicin combination effectively enhanced cancer cell death by impeding in vitro propagation and invasive ability. In addition, it led to an increase in doxorubicin accumulation and triggered apoptosis by arresting the cell cycle at the G2/M phase. Other observed effects included a decrease in the multi-drug resistance (MDR) carrier P-glycoprotein (P-gp) and TG2, a tumor survival factor. Augmented quantities of molecules promoting apoptosis such as Bak1 and caspase-3 and enhanced lipid peroxidation were also detected. Our findings in the cell model suggest that DHA can be further investigated as a natural compound to be used alongside doxorubicin in the treatment of breast cancer that is unresponsive to chemotherapy.

Breast cancer (BC) is the most common malignancy worldwide and has a poor prognosis, because it begins in the breast and disseminates to lymph nodes and distant organs. While invading, BC cells acquire aggressive characteristics from the tumor microenvironment through several mechanisms. Thus, understanding the mechanisms underlying the process of BC cell invasion can pave the way towards the development of targeted therapeutics focused on metastasis. We have previously reported that the activation of CD44 receptor with its major ligand hyaluronan (HA) promotes BC metastasis to the liver in vivo. Next, a gene expression profiling microarray analysis was conducted to identify and validate CD44-downstream transcriptional targets mediating its pro-metastatic function from RNA samples collected from Tet CD44-induced versus control MCF7-B5 cells. We have already validated a number of novel CD44-target genes and published their underlying signaling pathways in promoting BC cell invasion. From the same microarray analysis, Integrin subunit beta 1 binding protein 1 ( ITGB1BP1 ) was also identified as a potential CD44-target gene that was upregulated (2-fold) upon HA activation of CD44. This report will review the lines of evidence collected from the literature to support our hypothesis, and further discuss the possible mechanisms linking HA activation of CD44 to its novel potential transcriptional target ITGB1BP1 .

No abstract

Studies have reported inconsistent results for the relationship between body composition and bone mineral density (BMD) among women, especially those with a high rate of obesity. This study aims to examine the association between BMD and body composition among Qatari women. A cross-sectional study, using data from the Qatar Biobank (QBB), was conducted on 2,000 Qatari women aged 18 and over. Measurements were taken by dual-energy X-ray absorptiometry (DEXA) for body composition [visceral fat and android fat (AF)], gynoid fat (GF), trunk fat, total fat mass (TFM), total lean mass (LM) and bone mineral density (BMD), including the lumber spine, neck, femur and total body. The participants were divided into groups of normal and low BMD, based on their T-score. Non-linear regression analysis using the restricted cubic spline method was performed according to the T-score of the total BMD for the fat mass variables. Women with a low BMD (T-score <-1) had significantly lower body composition indicators. LM was positively correlated with BMD at the spine (r = 0.29, p < 0.001), neck (r = 0.32, p < 0.001), and femur (r = 0.28, p < 0.001), as well as total BMD (r = 0.29, p < 0.001) and T-score (r = 0.31, p < 0.001), while the correlatio between TFM and BMD was negative and weak (r = −0.05, <0.017). Results of the non-linear regression indicated that components of fat distribution (TFM, AF, GF and trunk fat) were positively associated with total body T-score. In the adjusted non-liner regression, only a slight increase in T-score was recorded with an increase in FM. The association between FM and BMD was non-linear, suggesting that FM may not be a strong protector of bones among women with high rate of obesity.

No abstract