Nefise Ülkü Karabay Yavaşoğlu

Parkinson’s Disease (PD) is the second most common neurodegenerative ailment, manifesting with motor symptoms such as tremor, bradykinesia, muscular rigidity, and postural instability, resulting fr...

Breast cancer remains one of the most common malignancies affecting women worldwide. Despite the effectiveness of traditional chemotherapeutic agents such as 5‐fluorouracil (5‐FU), their lack of selectivity often results in damage to healthy tissues, leading to undesirable adverse effects. The aim of this study was to modify 5‐FU with mannose containing 1,2,3‐triazole compound to reduce its toxic effect, and to investigate the anticancer properties of the resulting 5‐FU derivative (5‐FUD‐Man) in ER‐positive MCF‐7 breast cancer cells. Our results demonstrated that while 5‐FU caused significant cytotoxicity in both cancerous and healthy cells, 5‐FUD‐Man showed selective cytotoxicity, with minimal effects on MCF‐10A cells. Furthermore, immunofluorescence staining results indicated that 5‐FUD‐Man was more strongly activated apoptosis (Caspase‐3, AIF), autophagy‐mediated (LC3B), and stress‐associated signaling pathways (ERK1/2) in MCF‐7 cells compared to 5‐FU. These findings suggest that the combined use of carbohydrate‐based targeting via mannose and a bioactive triazole compound may enhance the selectivity and therapeutic efficacy of 5‐FU‐based treatments in breast cancer. Overall, 5‐FUD‐Man appears to be a promising candidate for further development as a more targeted and potentially safer therapeutic strategy.

Background/Objectives: Cisplatin (CDDP) is widely used in the treatment of non-small cell lung cancer (NSCLC); however, its clinical efficacy is limited by severe systemic toxicity. Hyaluronic acid (HA) modification enables the targeting of CD44-overexpressing cancer cells, enhances biocompatibility, provides controlled drug release, and prolongs systemic circulation. This study aimed to develop high-molecular-weight hyaluronic acid-modified, cisplatin-loaded mesoporous silica nanoparticles (HA-MSN-CDDP) to selectively target CD44-overexpressing lung adenocarcinoma cells. Methods: HA-MSN-CDDP nanoparticles were synthesized via the sol–gel method and characterized by FTIR, DLS, SEM, and TEM methods. Antitumor efficacy was evaluated using both in vitro and in vivo xenograft lung cancer models in mice. Results: HA modification enabled controlled and sustained release of cisplatin from the HA-MSN-CDDP drug delivery system. Through HA-mediated receptor-dependent endocytosis, the nanoparticles exhibited enhanced cellular uptake and selective cytotoxicity toward CD44-positive cells. HA-MSN-CDDP significantly reduced the cytotoxic, genotoxic, and oxidative stress effects of free cisplatin on healthy cells while markedly enhancing apoptosis in A549-Luc-C8 cells. The system showed excellent hemocompatibility, supporting its potential for intravenous use. In vivo, HA-MSN-CDDP effectively suppressed tumor growth, mitigated lipid peroxidation, and preserved antioxidant enzyme activities (SOD and CAT) in major organs. Histological analyses confirmed reduced cisplatin-induced nephrotoxicity. Conclusions: HA-MSN-CDDP demonstrates strong potential as a targeted chemotherapeutic platform for NSCLC, combining high antitumor efficacy with reduced systemic toxicity.

Salvia argentea L. (Lamiaceae) is a medicinal plant originating from the Mediterranean region and has been used since ancient times for the treatment of various diseases. This study aimed to determine the phytochemical composition of S. argentea L. ethanol extract and to evaluate its in vitro and in vivo anti-inflammatory activity and its acute oral toxicity. The chemical constituents of the ethanol extract prepared from the aerial parts of the plant were identified using HPLC. The in vitro anti-inflammatory activity of the extract was evaluated in LPS-stimulated murine macrophage RAW 264.7 cells and the human monocytic cell line THP-1 by measuring the levels of nitric oxide (NO), pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Acute toxicity of the extract was assessed in accordance with OECD guideline no 423. In vivo anti-inflammatory activity was evaluated based on the inhibition of 1% carrageenan-induced paw edema in rats. Serum CRP levels as an inflammatory marker, were measured via ELISA. Histological and immunohistochemical assessments were performed to identify tissue changes in the paw. HPLC profiling revealed that the extract contained rosmarinic acid (11.334 µg/mg dry extract), and salvigenin (2.74 µg/mg of dry extract) as major compounds. The extract significantly inhibited the production of NO, IL-1β, IL-6, and TNF-α without affecting cell viability. In vivo, the extract treatment exhibited a dose-dependent reduction in paw edema and serum CRP levels, along with notable histological improvements. Administration of the extract resulted in dose-dependent decreases of NF-κB expressions in the paw tissues. No signs of acute toxicity were observed (oral LD₅₀ > 2000 mg/kg). These findings suggest that S. argentea L. ethanol extract possesses significant anti-inflammatory potential supporting its possible development as a natural therapeutic agent for inflammatory disorders.

This study aimed to demonstrate the protective effect of the racemic form of gossypol ((±)-gossypol) on Ehrlich’s solid carcinoma (ESC) model as a syngeneic breast cancer model. In the study, solid tumors developed in 100 % of BALB/c mice in the tumor control group, no tumor development was observed in the group treated with (±)-gossypol prior to tumor cell implantation, and tumor formation was determined as 28.6 % in the post-implantation gossypol treatment group. (±)-Gossypol treatment significantly reduced VEGF expression, indicating a potent anti-angiogenic effect. In the tumor control group, VEGF expression was observed to be markedly intense and extensively distributed across the tumor tissue. Conversely, in the post-implantation gossypol treatment group, VEGF expression was assessed to be significantly lower in comparison to the tumor control group. Administration of (±)-gossypol (40 mg/kg/day ip) for five consecutive days was well tolerated, with no observable signs of systemic toxicity, such as >5 % weight loss or behavioral abnormalities on mice. These findings revealed that (±)-gossypol, in addition to its tumor suppressive effect, can inhibit pro-angiogenic effects of Ehrlich’s ascites carcinoma (EAC) cells and have a protective effect in breast cancer.

5‐Fluorouracil (5‐FU) is one of the first‐line chemotherapeutic agents used in systemic therapy of solid tumors. However, several challenges restrict the use of 5‐FU such as serious side effects and short plasma half‐life. Because carbohydrates and 1,2,3‐triazoles have various biological activities, they have been extensively used in medicine to obtain more effective anticancer drugs in recent years. The aim of this study is to modify 5‐FU with carbohydrates containing 1,2,3‐triazole compounds to reduce its toxic effect, and to reveal the anticancer properties of the obtained 5‐FU derivatives. These derivatives (5‐FU‐I, 5‐FU‐II, and 5‐FU‐III) revealed dose‐dependent cytotoxic effects on CaCo‐2, PANC‐1, and A549 cancer cells. It was determined that cytotoxic effects of the 5‐FUs change dependent on used carbohydrate types, cell lines, and administered doses. These derivatives showed apoptotic and necrotic cell deaths which used to destroy the cancer cells. 5‐FUs showed no genotoxic effect in the bacterial reverse mutasyon assay. They demonstrated strong antiangiogenic properties in the HET‐CAM test. In silico study results demonstrated that carbohydrate modification can increase half‐life and clearance, also decrease side effects of 5‐FU. In silico data supported the in vitro findings and results demonstrated 5‐FU derivatives were better drug candidates. Our results reveal that 5‐FUs derivatives modified carbohydrates containing 1,2,3‐triazole compounds have potential in cancer therapy.