Background: The migration of tumor cells is critical in spreading cancers through the lymphatic nodes and circulatory systems. Although arachidonic acid (AA) and its soluble metabolites have been shown to induce the migration of breast and colon cancer cells, the mechanism by which it induces such migration has not been fully understood. Objective: The effect of AA on migratory responses of the MDA-MB-231 cell line (a triple-negative breast cancer cell) was examined and compared with MCF-7 (estrogen-receptor positive) breast cancer cells to elucidate the mechanism of AA-induced migration. Methods: Migrations of breast cancer cells were examined with the help of wound-healing assays. AA-induced eicosanoid synthesis was monitored by RP-HPLC. Cellular localizations of lipoxygenase and lipid rafts were assessed by immunoblot and confocal microscopy. Results: AA treatment stimulated the synthesis of leukotriene B4 (LTB4) and HETE-8, but lowered the levels of prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and HETE-5 in MDA-MB-231 cells. Further analysis indicated that AA increased the expression of 5-lipoxygenase (5-LOX) in this cell line and inhibiting its expression by small molecule inhibitors lowered the production of LTB4 and reduced migration. In contrast, MCF-7 cells did not show any appreciable changes in eicosanoid synthesis, 5-LOX expression, or cellular migration. Conclusion: Our results suggest that AA treatment activates the BLT1 receptor (present in membrane microdomains) and stimulates the synthesis of LTB4 production, which is likely to be associated with the migration of MDA-MB-231 cells.
Although cisplatin is considered as an effective anti-cancer agent, it has shown limitations and may produce toxicity in patients. Therefore, we synthesized two cis-dichlorideplatinum(II) compounds (13 and 14) composed of meta- and para-N,N-diphenyl pyridineamine ligands through a reaction of the amine precursors and PtCl2 with respective yields of 16% and 47%. We hypothesized that compounds 13 and 14, with lipophilic ligands, should transport efficiently in cancer cells and demonstrate more effectiveness than cisplatin. When tested for biological activity, compounds 13 and 14 were found to inhibit the growth of MCF 7 and MDA-MB-231 cells (IC50s 1 ± 0.4 μM and 1 ± 0.2 μM for 13 and 14, respectively, and IC50 7.5 ± 1.3 μM for compound 13 and 1 ± 0.3 μM for compound 14). Incidentally, these doses were found to be lower than cisplatin doses (IC50 5 ± 0.7 μM for MCF 7 and 10 ± 1.1 μM for MDA-MB-231). Similar to cisplatin, 13 and 14 interacted with DNA and induced apoptosis. However, unlike cisplatin, they blocked the migration of MDA-MB-231 cells suggesting that in addition to apoptotic and DNA-binding capabilities, these compounds are useful in blocking the metastatic migration of breast cancer cells. To delineate the mechanism of action, computer-aided analyses (DFT calculations) were conducted for compound 13. Results indicate that in vivo, the pyridineamine ligands are likely to dissociate from the complex, forming a platinum DNA adduct with anti-proliferative activity. These results suggest that complexes 13 and 14 hold promise as potential anti-cancer agents.
Introduction: Methamphetamine (meth) is a stimulant increasing in use and its prevalence has not yet been determined on the Mexico-US border. Few studies highlight gender differences in meth use, trajectory, and initiation by gender. Ciudad Juárez, Mexico, across the border from El Paso, TX, has an established stimulant using population and lies on drug trafficking route. This study assessed gender differences in drug and meth use patterns among people meth people use meth. Materials and Methods: This cross-sectional study included 150 people with recent meth use, age 21 years or older, and living in Ciudad Juárez. Measures collected included sociodemographic characteristics, cross-border mobility, drug, and meth use characteristics. Statistically (P<0.05) and marginally (P<0.10) significant gender differences were determined using appropriate bivariate tests. Results: The sample included 45 cisgender women, 5 transgender women, and 100 cisgender men with a mean age of 30.9 years. Men had significantly higher rates of snorting meth by nose in powder or rock forms, while trans/women more frequently using meth in pill form. Men had higher rates of crossing the border for work, with meth, and to obtain meth. Trans/women reported higher rates of acquiring meth from their main sexual partner and initiating meth use in Mexico. Discussion: There are gender differences in patterns of meth use and initiation. Conclusions: A sample of people who use meth in the general population can be achieved. These findings point to a need for evidence-based meth use reduction treatment programs that are culturally appropriate and tailored for gender.
Minority young adults in U.S.-Mexico border communities are at high risk for Substance Abuse(SA), and infection with the Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV). With funding from the Substance Abuse and Mental Health Services Administration (SAMHSA), a Hispanic Serving institution on the U.S.-Mexico border in partnership with two community-based organizations implemented integrated SA, HIV and HCV prevention among minority young adults on collegecampus and surrounding communities. Six focus groups (3 on campus and 3 in surrounding communities; N=48) were conducted with individuals 18 -24 years of age to inform priority population needs and project strategic plan. Five themes emerged from campus and community feedback: (i) types of substances used and local norms shaping such substance abuse; (ii) risky sexual behaviors shaped by stigma, cultural and gender norms, (iii) gaps in HIV and HCV knowledge, (iv) barriers to access and utilization of prevention services, and (v) suggestions for effective SA, HIV and HCV prevention. The implications for addressing U.S.-Mexico border regional norms shaping SA, HIV and HCV risk behaviors among minority young adultsfor interventions that engage minority young adults' on and off campus networks are discussed.
Ethnic and sexual minority young adults in El Paso, Texas, are at high risk for substance use, human immunodeficiency virus (HIV), and hepatitis C virus (HCV). In 2014, a Hispanic-serving higher education institution partnered with two community-based organizations to implement integrated substance use interventions and HIV and HCV prevention among young adults on campus and in surrounding communities. Among the 95 young adults, aged 18–24 years, who responded to a needs assessment survey, 91.5% were Hispanic, 53.7% were female, and 27.4% were sexual or gender minorities (SGMs) as defined by behavior and identity. SGMs had significantly higher rates of current smoking, drinking when bored, and of being told they had a drinking problem. Compared with the other young adult survey respondents, SGMs had lower health risk perceptions for tobacco, alcohol, and marijuana use and reported similar or higher rates of lifetime drug use during sex and higher rates of HIV risk behaviors. Study findings have implications for including measures for sexual orientation and gender identity in substance use studies, examining regional and cultural norms that may intersect to shape substance use among SGMs, and incorporating unique risk contexts for SGMs in interventions for substance use.
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