Yadav Sneha, Arman Mohammad, Kumar Anurag, Sonkar Archana Bharti, Shrivastava Neeraj Kumar, Singh Jyoti, Ansari Mohd Nazam, Aldossary Sara A, Saeedan Abdulaziz S, Kaithwas Gaurav
Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow, U.P. 226 025, India.
Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia.
J Genet Eng Biotechnol. 2025 Jun;23(2):100480. doi: 10.1016/j.jgeb.2025.100480. Epub 2025 Mar 23.
The ketogenic diet (KD) has been emphasized as a complementary strategy for management of several clinical conditions including cancer. Therefore, in this study we explored the effect of KD in mammary gland carcinoma through in-vitro and in-vivo studies. In-vitro studies were performed on MCF-7 and MDA-MB-231 cells with different experimental conditions such as high glucose (HG), low glucose (LG) and no glucose(NG) in conjugation with β-hydroxy butyrate(BHB) treatment. The MTT assay revealed that glucose deprivation alongwith BHB(10 mM) treatment significantly reduces the viability of MDA-MB-231 cells as compared to MCF-7 cells. Moreover, apoptotic and antiproliferative potential (via AO/EtBr, JC-1, cell migration assay) were analyzed on MDA-MB-231 cells which indicate that NG with BHB treatment induce cell death.Furthermore, we investigated the in-vivo anticancer efficacy against DMBA-induced mammary gland carcinoma in female Wistar rats. KD treatment effectively restored autonomic dysfunction, altered mammary gland morphology and histology; as evident through decrease in lobules, alveolar bud, restoration of the surface architecture and loss of tumor micro-vessels. The altered levels of antioxidants such as TBARs(0.85 ± 0.19 nM of MDA/µg of protein), SOD(2.26 ± 0.05 U/µg of protein), PC(41.36 ± 2.94 µM/µg of protein), GSH(10.58 ± 3.08 µM/µg of protein) were also restored after KD treatment. Overall findings suggested, that deprived glucose concentration alongwith BHB can impart antiproliferative and apoptotic effect as observed through MDA-MB-231cells. Moreover, KD also diminished the carcinogenic effects of DMBA in albino wistar rats. In view of above, the KD was utilised as adjuvant therapy in the management of mammary gland carcinoma,possibly by providing unfavourable microenvironment for highly proliferating tumour cells due deficiency of quickly available glucose.
生酮饮食（KD）已被强调为包括癌症在内的多种临床病症管理的一种辅助策略。因此，在本研究中，我们通过体外和体内研究探索了KD对乳腺癌的影响。在MCF-7和MDA-MB-231细胞上进行了体外研究，采用了不同的实验条件，如高糖（HG）、低糖（LG）和无糖（NG），并结合β-羟基丁酸（BHB）处理。MTT分析显示，与MCF-7细胞相比，葡萄糖剥夺联合BHB（10 mM）处理显著降低了MDA-MB-231细胞的活力。此外，对MDA-MB-231细胞进行了凋亡和抗增殖潜力分析（通过AO/EtBr、JC-1、细胞迁移分析），结果表明无糖联合BHB处理可诱导细胞死亡。此外，我们研究了KD对雌性Wistar大鼠二甲基苯并蒽（DMBA）诱导的乳腺癌的体内抗癌疗效。KD治疗有效地恢复了自主神经功能障碍，改变了乳腺的形态和组织学；通过小叶减少、肺泡芽减少、表面结构恢复和肿瘤微血管消失可以明显看出。KD治疗后，抗氧化剂如硫代巴比妥酸反应物（TBARs，0.85±0.19 nM丙二醛/μg蛋白质）、超氧化物歧化酶（SOD，2.26±0.05 U/μg蛋白质）、谷胱甘肽过氧化物酶（PC，41.36±2.94 μM/μg蛋白质）、谷胱甘肽（GSH，10.58±3.08 μM/μg蛋白质）的水平也得到了恢复。总体研究结果表明，如通过MDA-MB-231细胞观察到的那样，剥夺葡萄糖浓度联合BHB可产生抗增殖和凋亡作用。此外，KD还减弱了DMBA对白化Wistar大鼠的致癌作用。鉴于上述情况，KD可作为辅助治疗用于乳腺癌的管理，可能是通过因快速可用葡萄糖缺乏为高度增殖的肿瘤细胞提供不利的微环境。
