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β-Sitosterol from Allium cepa Seeds Exerts Dual-Target Anticancer Activity Against NFKB1 and STAT3 in Triple-Negative Breast Cancer: An Integrated In Silico and In Vitro Investigation | ||
| Iranian Journal of Analytical Chemistry | ||
| دوره 12، شماره 2، اردیبهشت 2026، صفحه 12-28 اصل مقاله (1.05 M) | ||
| نوع مقاله: Full research article | ||
| شناسه دیجیتال (DOI): 10.30473/ijac.2026.77606.1345 | ||
| نویسندگان | ||
| Sholeh Javadi؛ Somayeh Farahmand* ؛ Helia Bayat؛ Reza HajiHosseini؛ Sima Nasri | ||
| Department of Biology, Payame Noor University, Tehran, Iran. | ||
| چکیده | ||
| Triple-negative breast cancer (TNBC) lacks targetable receptors, rendering conventional chemotherapy the sole standard of care despite its associated toxicity and acquired resistance. The constitutively activated NF-κB and STAT3 signaling axes represent mechanistically interdependent oncogenic drivers in TNBC, making their simultaneous inhibition a compelling therapeutic strategy. β-Sitosterol, the predominant phytosterol of Allium cepa seeds, has demonstrated broad antiproliferative properties; however, its capacity for dual-target engagement against NFKB1 and STAT3 has not been systematically characterized. GC–MS profiling of A. cepa seed oil identified β-sitosterol as the principal constituent (80.45%). Computational ADMET analysis, Human Protein Atlas-based immunocytochemical target validation, and Auto Dock Vina molecular docking against NFKB1 (PDB: 5AX3) and STAT3 (PDB: 7LET) were performed. Anticancer activity was evaluated in MDA-MB-231 cells via MTT assay, with apoptotic mechanism characterized by Annexin V-FITC/PI flow cytometry. β-Sitosterol demonstrated favorable drug-likeness with predicted mitochondrial localization and absence of mutagenicity. Docking yielded binding energies of −7.0 and −6.7 kcal/mol for STAT3 and NFKB1, respectively, driven by hydrophobic interactions. MTT assay revealed concentration-dependent cytotoxicity (IC₅₀ = 39.56 µM; 72 h; F = 113.8, p < 0.0001). Flow cytometry confirmed significant induction of early (30.7 ± 2.5%) and late apoptosis (20.3 ± 4.4%) versus negligible baseline levels in controls. β-Sitosterol exhibits dual computational binding affinity for NFKB1 and STAT3 alongside potent pro-apoptotic activity in TNBC cells, establishing a mechanistic foundation for its further translational development. | ||
| کلیدواژهها | ||
| β-sitosterol؛ Triple-negative breast cancer؛ NFKB1؛ STAT3؛ Apoptosis؛ MDA-MB-231 | ||
| عنوان مقاله [English] | ||
| بتا-سیتوسترول استخراجشده از دانههای پیاز (Allium cepa) از طریق مهار همزمان NFKB1 و STAT3 با اثر ضد سرطانی دو محوره در سرطان پستان سهگانه منفی(TNBC): بررسی یکپارچه سلیکو و آزمایشگاهی | ||
| نویسندگان [English] | ||
| شعله جوادی؛ سمیه فرهمند؛ هلیا بیات؛ رضا حاجی حسینی؛ سیما ناصری | ||
| گروه زیست شناسی، دانشگاه پیام نور، تهران، ایران | ||
| چکیده [English] | ||
| سرطان پستان سهگانه منفی (TNBC) فاقد گیرندههای قابل هدف درمانی است و شیمیدرمانی متداول، علیرغم سمیت بالا و مقاومت اکتسابی، تنها گزینه استاندارد درمانی محسوب میشود. محورهای سیگنالینگ NF-κB و STAT3 در TNBC بهطور مداوم فعال هستند و بهعنوان محرکهای انکوژنیک متقابل شناخته میشوند. ازاینرو، مهار همزمان آنها یک راهبرد درمانی جذاب محسوب میگردد. بتا-سیتوسترول، فیتوسترول غالب دانههای Allium cepa، خواص ضدتکثیری گستردهای نشان میدهد؛ با این حال، توانایی آن در تعامل همزمان با NFKB1 و STAT3 بهصورت سیستماتیک بررسی نشده است. پروفایلسازی GC–MS روغن دانه A. cepa، بتا-سیتوسترول را بهعنوان ترکیب اصلی با سهم ۸۰٪ شناسایی کرده است. آنالیز محاسباتی ADMET، اعتبارسنجی ایمونوسیتوشیمیایی اهداف از پایگاه داده Human Protein Atlas، و داکینگ مولکولی با AutoDock Vina علیه NFKB1 (PDB: 5AX3) و STAT3 (PDB: 7LET) انجام گرفت. فعالیت ضدسرطانی در سلولهای MDA-MB-231 از طریق سنجش MTT ارزیابی شد و مکانیسم آپوپتوز با فلوسیتومتری Annexin V-FITC/PI مشخص گردید. بتا-سیتوسترول دارای پروفایل دارویی مطلوب، توزیع پیشبینیشده در میتوکندری، و فقدان جهشزایی ژنوتوکسیک گزارش شد. داکینگ انرژیهای اتصال 7.0- و 6.7- کیلوکالری بر مول را بهترتیب برای STAT3 و NFKB1 نشان داد که عمدتاً از طریق برهمکنشهای هیدروفوبیک ایجاد میشوند. سنجش MTT سمیت سلولی وابسته به غلظت را آشکار کرد (IC₅₀ = 39.56 µM؛ 72h؛ F = 113.8، p < 0.0001). فلوسیتومتری القای معنادار آپوپتوز اولیه (30.7 ± 2.5%) و آپوپتوز دیررس (20.3 ± 4.4%) را در مقایسه با سطوح پایه ناچیز در گروه کنترل تأیید کرد. بتا-سیتوسترول همراه با قدرت اتصال محاسباتی دوگانه به NFKB1 و STAT3، فعالیت آپوپتوزی قوی در سلولهای TNBC از خود نشان میدهد و بدینترتیب پایه مکانیستی برای توسعه ترجمانی بیشتر آن بهعنوان داوطلب درمانی دو محوره در سرطان پستان سهگانه منفی فراهم میآورد. | ||
| کلیدواژهها [English] | ||
| بتا-سیتوسترول, سرطان پستان سهگانه منفی, NFKB1, STAT3, آپوپتوز, MDA-MB-231 | ||
| مراجع | ||
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