Triple-negative breast cancer (TNBC) is one of the deadliest forms of breast cancer. Investigating alternative therapies to increase survival rates for this disease is essential. To this end, the cytotoxic effects of the prenylated stilbenoids arachidin-1 (A-1) and arachidin-3 (A-3), and non-prenylated resveratrol (RES) were evaluated in human TNBC cell lines as potential adjuvants for paclitaxel (Pac). A-1, alone or in combination with Pac, showed the highest cytotoxicity in TNBC cells. Apoptosis was further evaluated by measuring key apoptosis marker proteins, cell cycle arrest, and intracellular reactive oxygen species (ROS) generation. Furthermore, the cytotoxic effect of A-1 combined with Pac was also evaluated in a 3D spheroid TNBC model. The results showed that A-1 decreased the Pac IC50 approximately 2-fold in TNBC cells. The synergistic combination of A-1 and Pac arrested cells in G2/M phase and activated p53 expression. In addition, the combined treatment increased intracellular ROS generation and induced apoptosis. Importantly, the combination of A-1 with Pac inhibited TNBC spheroid growth. Our results demonstrated that A-1 in combination with Pac inhibited cell proliferation, induced apoptosis through mitochondrial oxidative stress, and reduced TNBC spheroid growth. These findings underscore the impactful effects of the prenylated stilbenoid A-1 as a novel adjuvant for Pac chemotherapy in TNBC treatment.
Breast cancer is the most prevalent type of cancer among women worldwide. Triple‐negative breast cancer (TNBC) is unresponsive to typical hormonal treatments causing it to be one of the deadliest forms of breast cancer. Investigating alternative therapies to increase survival rates for this disease is essential. This study aims to examine the role of prenylated stilbenoids as an adjuvant for paclitaxel, a chemotherapeutic drug with severe side effects. To produce prenylated stilbenoids, hairy root cultures of peanut were co‐treated with elicitors and further purified via semi‐preparative high performance liquid chromatography. The cytotoxicity of prenylated stilbenoids was studied in TNBC cell lines MDA‐MB‐231 and MDA‐MB‐436 and the non‐cancerous cell line MCF‐10A. At low micromolar concentrations, the prenylated stilbenoid arachidin‐1 showed no significant cytotoxicity in the non‐cancerous cell line, whereas it was cytotoxic in the TNC cell lines. High cytotoxicity levels correlated with increased levels of the apoptosis markers caspase‐3 and caspase‐7. Arachidin‐1 also decreased the IC50 of paclitaxel by approximately 4‐fold and blocked cell division in S and G2‐M phases in the TNBC cells. Furthermore, paclitaxel combined with arachidin‐1 induced apoptosis through the intrinsic pathway by activation of caspase‐9. This highlights the significance of continuing research with prenylated stilbenoids in TNBC. Current studies focus on elucidating the signaling pathways affected by these compounds in TNBC cells to advance our understanding of the anticancer mechanisms of these natural products.
According to CDC influenza estimates, the flu infects ~40 million people and causes 24,000 to 60,000 deaths in the United States annually. Vaccination can be highly effective but is often a neglected tool for preventing infection. In this project, three methods were developed to compare an individual’s reported self-history of influenza infection to the types and amounts of nasal bacteria collected by nasal swab to assess if certain bacteria may correlate with less history of influenza infection. These three methods quantified species from four genera of bacteria - Staphylococcus, Micrococcus, Streptococcus and Haemophilus - and compared the amounts of each type of bacteria with participant survey answers regarding their history of influenza infection. In Method 1, a disk diffusion test with bacitracin distinguished isolates of Staphylococcus from Micrococcus. Higher ratios of Staphylococcus to Micrococcus were found in individuals less susceptible to influenza (p = 0.003). In Method 2, S. pyogenes and S. pneumoniae were distinguished based on their hemolytic patterns. A higher proportion S. pneumoniae significantly correlated with more history of influenza (p = 0.002). In Method 3, total numbers of Staphylococcus spp. and H. influenzae were compared. More frequent H. influenzae significantly correlated with higher influenza frequency (p = 0.006). While all three methods indicate correlations between specific nasal bacteria and influenza susceptibility, Method 2 was the simplest and least expensive to perform. Commercialization of one or more of these methods could result in a simple and inexpensive test to identify at-risk individuals for influenza.
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