<p class="BodyText1">Hydroxybenzoate (HB) compounds have shown to modulate the morphology in human fibrosarcoma HT-1080 cells. The changes in HT-1080 cells showed marker signs of apoptosis, which included the condensation of nucleus, cell round, blebbing and the formation of apoptotic bodies. The different stages of apoptosis were assessed microscopically using different staining and immunohistochemical techniques, as well as scanning electron microscopy. In addition, HB compounds increased the expression of caspase-3, which is closely associated with the development of the modulation in HT-1080 cells that are undergoing the programmed cell death. Both acetyl salicylic acid (ASA) and HBZn compounds were dose and treatment duration dependent.</p>
Hydroxybenzoate (HB) compounds have shown their significance in inducing apoptosis in primary chronic lymphocytic leukemia (CLL) and cancer cell lines, including HT-1080. The current study focuses on assessing the effects of 2-, 3-and 4-hydroxybenzoate calcium (HBCa) compounds on MCF-10A, MDA-MB231 and MCF-7 epithelial breast cell lines. The HBCa-treated cells were examined using annexin V, to measure apoptosis in the three epithelial breast cell lines, after 48 h of treatment. The results indicated that 0.5 and 2.5 mmol/L of HBCa induced cell death in a dose-dependent manner. The induction of cell death in normal MCF-10A cells was found to be significantly less (p = 0.0003-0.0068), in comparison to the malignant cell lines (MDA-MB231 and MCF-7). HBCa compounds were also found to cause cell cycle arrest in the epithelial breast cells at G1/G0. Furthermore, HBCa compounds induced the upregulation of apoptotic proteins (p53, p21, Bax and caspase-3), as well as the downregulation of the anti-apoptotic protein Bcl-2, which may suggest that apoptosis is induced via the intrinsic pathway. reast cancer is a major global health issue that mainly affects women of all age groups. It is the most common cancer worldwide, with more cases in developing countries than in developed countries [1] . Breast cancer is the second leading cause of cancer death after lung cancer in developed countries (198,000 cases, 15.4%). Incidence rates continue to increase globally except in a few high-income countries. The estimated breast cancer incidents of less developed cases in 2012 were 883,000 (52.8%) and 788,000 more developed cancer cases, with mortality rates of 324,000 (62.1%) and 198,000 (37.9%), respectively [2] . In contrast, more than 60% of breast cancer patients survive in developed countries. Lower survival rates occur in developing countries due to the lack of early detection schemes and diagnosis [3] . Statistics related to breast cancer cases have attracted the attention of various researchers to effectively treat the cancer with chemotherapy. As part of this effort, a large number of compounds have been assessed for their anticancer potential in dif-B
Acetylsalicylic acid, or aspirin, is one of the most common non-steroidal anti-inflammatory drugs, which has been shown to have anti-cancer effects. However, high doses are needed making it unsuitable as an oncology agent. We have previously reported increased potency in a series of hydroxybenzoate zinc (HBZn) aspirin analogues. Here we show that 3-hydroxybenzoate magnesium (3-HBMg) and 4-hydroxybenzoate magnesium (4-HBMg) aspirin derivatives showed cytotoxic effects at doses as low as 1mM. At these concentrations, 3-HBMg and 4-HBMg aspirin increased the level of caspase-3, p53, Bax and decreased the expression of the anti-antiapoptotic protein, Bcl-2, in HT-1080 Human fibrosarcoma cells.
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