From fungistatic to cytotoxic: Nano-engineered griseofulvin triggers redox-mediated apoptosis in colon cancer Jihad Mahmoud Alsofany, Soha Osama Hassanin, Ahmad S. Kodous, Mohammed Aufy, Maha O. Mahmoud, Islam M. Adel, Mohamed A. El-Nabarawi, Eman Abdelhakeem European Journal of Pharmaceutical Sciences, 2026 Griseofulvin, a potent antifungal drug, has recently demonstrated potential anticancer activity in mammalian cancer cells. This study aims to comprehensively investigate the anti-cancer potential of griseofulvin encapsulated into nanospanlastics, focusing on enhanced cellular uptake, selectivity, and robust activation of multiple apoptotic pathways. Griseofulvin nanospanlastics were fabricated using a 2 3 full factorial experimental design with Span 60 as the non-ionic surfactant and Tween 80 as the edge activator. Nanospanlastics were characterized for vesicle size, size distribution, zeta potential, and entrapment efficiency. The statistically optimized formulation was selected for further physical characterization and investigation of its anticancer potential via cytotoxicity, selectivity assays, and analysis of molecular pathways (p53, Bax/Bcl-2, caspase 3, pAKT, VEGFR2, ROS). The optimized formulation exhibited circular morphology without any aggregation, 143.5±15.56 nm vesicle size, 0.739±0.021 size distribution, -30±0.99 mV zeta potential, 89.07±0.11% entrapment efficiency, and 30.2±0.14 g deformability index. In vitro drug release showed an improved drug dissolution rate, critical for cellular uptake. The optimized formulation attained exceptional therapeutic activity with a 2.29-fold improvement in cytotoxicity and an 8.1-fold enhancement in cancer cell selectivity compared to the free drug solution, while simultaneously modulating critical molecular pathways including p53 activation, Bax/Bcl-2, caspase 3, phosphorylated AKT (pAKT) inhibition, and VEGFR2. Most surprisingly, the study revealed an unexpected reduction in reactive oxygen species (ROS) levels, challenging conventional therapeutic paradigms and highlighting novel "redox paradox" mechanisms in cancer treatment. This comprehensive investigation highlights the remarkable apoptotic potential of nanosized griseofulvin, driven by enhanced cellular uptake, superior selectivity, and robust activation of multiple apoptotic pathways.
Design, Synthesis, Biological Evaluation, and In Silico Studies of Novel Furo[2,3-d]pyrimidine Derivatives as EGFR Inhibitors With Potential Antitumor Activity Samar I. Faggal, Walid E. Elgammal, Amr Sonousi, Amr M. Abdou, Soha O. Hassanin, Rasha A. Hassan Archiv Der Pharmazie, 2025 In the pursuit of developing targeted therapies, novel furo[2,3‐ d ]pyrimidine compounds were synthesized, incorporating the characteristic structural features of EGFR tyrosine kinase inhibitors. These compounds were screened for antiproliferative effects across 60 human cancer cell lines. Compound 3f was the most effective. Further evaluation at five concentrations to determine its GI 50 , TGI, and LC 50 . In vitro studies were conducted to evaluate its impact on EGFR signaling, cell cycle progression, apoptosis induction, and caspase‐3 activation in T‐47D cells. Compound 3f showed greater selectivity toward cancerous T‐47D cells over normal breast cells (MCF10a). Notably, compound 3f displayed potent EGFR inhibition at submicromolar levels, with an IC 50 of 0.121 ± 0.004 μM, which was comparable to the reference inhibitor, erlotinib. Further investigations revealed that compound 3f caused cell cycle arrest at the G2/M phase in T‐47D cells. Apoptosis analysis confirmed that compound 3f induced cell death through programmed cell death, with a nearly 19‐fold increase in total apoptosis. This apoptotic mechanism was validated by a substantial rise in active caspase‐3 levels. Molecular docking studies showed favorable binding of compound 3f within the EGFR active site. Molecular dynamics simulations further confirmed the stability of compound 3f within the active site over a 100‐ns simulation period, supporting its sustained interaction with key residues. Based on predictions of toxicity, compound 3f was predicted to possess a favorable safety profile across 30 potential toxicities. Encouraged by its strong anticancer efficacy and safety profile, compound 3f represents a compelling lead candidate for further development as a targeted treatment for breast cancer.
Withania somnifera Ameliorates Doxorubicin-Induced Nephrotoxicity and Potentiates Its Therapeutic Efficacy Targeting SIRT1/Nrf2, Oxidative Stress, Inflammation, and Apoptosis Amany Mohammed Mohmmed Hegab, Soha Osama Hassanin, Reham Hassan Mekky, Samah Sulaiman Abuzahrah, Alaaeldin Ahmed Hamza, Iman M. Talaat, Amr Amin Pharmaceuticals, 2025 Background: Doxorubicin (DOX) is a very powerful chemotherapy drug. However, its severe toxicity and potential for resistance development limit its application. Withania somnifera L. Dunal (WIT) has therapeutic capacities, including anti-inflammatory, antioxidant, and anticancer activities. This study investigates the preventative benefits of a standardized WIT extract against DOX-induced renal damage in vivo. We also investigate the synergistic effects of combining WIT and DOX to improve therapeutic efficacy in breast cancer cells (MCF7-ADR). Methods: This study employed an animal model where rats were administered 300 mg/kg/day of WIT orally for a duration of 14 days. Rats received DOX injections at a dose of 5 mg/kg, for a total of 15 mg, on the 6th, 8th, and 10th days. Results: Present results revealed that WIT reduced DOX-induced increase levels of blood urea and creatinine and the activity of kidney injury molecule-1. WIT also reduced renal tissue damage, oxidative stress, and levels of pro-inflammatory markers. WIT alleviated the effects of DOX on nuclear factor erythroid 2-related factor 2, heme oxygenase-1, and sirtuin 1 in the renal tissues. WIT modulated nuclear factor-κB activity and decreased apoptotic indicators. Furthermore, WIT improves DOX’s capacity to kill drug-resistant MCF7-ADR cells by arresting the cell cycle and promoting apoptosis. Chemical analysis of WIT root extract revealed 34 distinct compounds, including alkaloids, withanolides, flavanones, and fatty acids. Conclusions: These constituents synergistically contribute to WIT’s antioxidant, anti-inflammatory, and anti-apoptotic properties. In addition, they confirm its ability to reduce systemic toxicity while improving treatment efficacy.
Transdermal fluocinolone acetonide loaded decorated hyalurosomes cellulose acetate/polycaprolactone nanofibers mitigated Freund’s adjuvant-induced rheumatoid arthritis in rats Sammar Fathy ELhabal, Mohamed A. El-Nabarawi, Soha Osama Hassanin, Fatma E. Hassan, Samah S. Abbas, Sahar M. Gebril, Rofida Albash Journal of Pharmaceutical Investigation, 2025 Purpose This study aimed to develop a transdermal delivery system for fluocinolone acetonide (FLA), a corticosteroid used in treating inflammatory conditions like rheumatoid arthritis (RA), to overcome the limitations of oral administration, such as poor solubility and bioavailability. Methods FLA-loaded PEG decorated hyalurosomes (FLA-PHs) were fabricated using ethanol injection, incorporating various Brij® surfactants and different amounts of hyaluronic acid (HA) based on a full factorial design. The impact of independent variables, HA amount (mg) (X1) and Brij type (X2) were inspected for entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP). The optimum FLA-PHs were then incorporated into ε-polycaprolactone (PCL) and cellulose acetate (CA) nanofibers to enhance sustained transdermal delivery (FLA-NFs). Results The optimum FLA-PHs exhibited EE% of 83.58 ± 0.69%, PS of 169.00 ± 1.41 nm, and ZP of -22.90 ± 0.14 mV. Morphological assessment of FLA-NFs showed promising results in terms of surface roughness. In a Freund-induced rat model of adjuvant-induced arthritis, transdermal treatment with FLA-NFs significantly improved joint histopathological analyses. Furthermore, it suppressed inflammatory markers such as mTORC1, TNF-α, and NF-κB while upregulating TRIM24 and the anti-inflammatory IL-10. Conclusion FLA-NFs present a promising strategy for enhancing the transdermal delivery of FLA for managing RA, offering potential improvements in efficacy and reduced systemic side effects compared to conventional oral administration.
Therapeutic approaches for septicemia induced by multidrug-resistant bacteria using desert-adapted plants Nesreen Safwat, Rana Elshimy, Soha O. Hassanin, Arwa Ramadan El-manakhly, Abdullah N. Noaf, Abdallah Tageldein Mansour, Fatma Alshehri, Majid Alhomrani, Abdulhakeem S. Alamri, Mahmoud Mohammed Bendary Frontiers in Cellular and Infection Microbiology, 2025 AimSepticemia, a life-threatening condition, can arise when bacterial infections are left untreated, allowing the pathogens to spread into the bloodstream. Moreover, infections caused by MDR bacteria are particularly challenging, as they can persist and lead to septicemia even when treated with conventional antibiotics. This study aimed to address this crisis by investigating combination therapies using desert-adapted medicinal plant extracts, including Jasonia candicans (J. candicans), Cistanche tubulosa, Moltkiopsis ciliata, and Thymelea hirsuta, as alternative treatments. The goal was to develop new strategies to combat resistance and improve the management of septic patients.MethodologyIn this study, 400 blood samples from septic patients were analyzed to identify Gram-negative bacterial isolates. Antimicrobial resistance patterns were assessed using standard susceptibility tests. Medicinal plant extracts were evaluated for antimicrobial activity using agar diffusion and broth microdilution assays, while COX-1 and COX-2 inhibition and antioxidant activity were measured using in vitro assays. Histopathological examinations were conducted on treated mice to assess tissue damage and response.ResultsWe observed a high prevalence of E. coli and K. pneumoniae among septic patients. Multidrug resistance was widespread, with many isolates showing high resistance to various antibiotics, although all were susceptible to colistin. Evaluation of desert-adapted plant extracts revealed that J. candicans exhibited the most potent antimicrobial activity and the strongest COX-1 and COX-2 inhibitory activities, as well as antioxidant effects, compared to other extracts and Celecoxib, with a concentration required to achieve 50% enzyme inhibition (IC50) value of 71.97 μg/mL for antioxidant activity. Moreover, the combination of this extract with amikacin showed a synergistic effect, significantly enhancing antimicrobial efficacy and converting over 50% of amikacin-resistant strains to sensitive phenotypes. Histopathological analysis of mice showed that the combination of J. candicans extract and amikacin resulted in reduced severity of pulmonary lesions and splenic damage compared to amikacin alone.ConclusionWe highlighted the potential of J. candicans extracts as combination therapies alongside traditional antibiotics for combating MDR Gram-negative infections, due to their superior antimicrobial, anti-inflammatory, and antioxidant properties.
Combining In Vitro, In Vivo, and Network Pharmacology Assays to Identify Targets and Molecular Mechanisms of Spirulina-Derived Biomolecules against Breast Cancer Soha Osama Hassanin, Amany Mohammed Mohmmed Hegab, Reham Hassan Mekky, Mohamed Adel Said, Mona G. Khalil, Alaaeldin Ahmed Hamza, Amr Amin Marine Drugs, 2024 The current research employed an animal model of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland carcinogenesis. The estrogen receptor-positive human breast adenocarcinoma cell line (MCF-7) was used for in vitro analysis. This was combined with a network pharmacology-based approach to assess the anticancer properties of Spirulina (SP) extract and understand its molecular mechanisms. The results showed that the administration of 1 g/kg of SP increased the antioxidant activity by raising levels of catalase (CAT) and superoxide dismutase (SOD), while decreasing the levels of malonaldehyde (MDA) and protein carbonyl. A histological examination revealed reduced tumor occurrence, decreased estrogen receptor expression, suppressed cell proliferation, and promoted apoptosis in SP protected animals. In addition, SP disrupted the G2/M phase of the MCF-7 cell cycle, inducing apoptosis and reactive oxygen species (ROS) accumulation. It also enhanced intrinsic apoptosis in MCF-7 cells by upregulating cytochrome c, Bax, caspase-8, caspase-9, and caspase-7 proteins, while downregulating Bcl-2 production. The main compounds identified in the LC-MS/MS study of SP were 7-hydroxycoumarin derivatives of cinnamic acid, hinokinin, valeric acid, and α-linolenic acid. These substances specifically targeted three important proteins: ERK1/2 MAPK, PI3K-protein kinase B (AKT), and the epidermal growth factor receptor (EGFR). Network analysis and molecular docking indicated a significant binding affinity between SP and these proteins. This was verified by Western blot analysis that revealed decreased protein levels of p-EGFR, p-ERK1/2, and p-AKT following SP administration. SP was finally reported to suppress MCF-7 cell growth and induce apoptosis by modulating the PI3K/AKT/EGFR and MAPK signaling pathways suggesting EGFR as a potential target of SP in breast cancer (BC) treatment.
