Exploring the Therapeutic Potential of β-Hydroxybutyrate (BHB) in Clear Cell Renal Cell Carcinoma: A Journey into Fat Browning, Autophagy, and Tumor Slimming

IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
Roya Rezaei, Asra Abdali Larki, Rosa Hosseinzadegan, Zahra Dashti, Saba Tarkashvand, Reihaneh Akhoondi, Morvarid Siri, Mesbah Shams, Alireza Monsef, Sanaz Dastghaib
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引用次数: 0

Abstract

This study delves into the therapeutic potential of β-hydroxybutyrate (BHB) in clear cell renal cell carcinoma (ccRCC), a cancer known for its complex pathogenesis and resistance to conventional treatments. The research specifically explores the impact of BHB on cell viability, autophagy induction, and lipid metabolism in Caki-1 cells. The findings reveal that BHB significantly reduces ccRCC cell viability, particularly under low-glucose conditions. The combination of glucose and BHB treatment activates autophagy pathways, as evidenced by increased expression of autophagy-related genes (Beclin-1, LC3IIβ, and ATG5) and decreased expression of P62 after 48 and 72 hours. Moreover, the combined therapy enhances lipid metabolism, as indicated by elevated expression of PGC-1α and UCP-1, along with upregulation of ACSL3 and CPT1A, which are associated with lipid droplet formation and facilitate lipid breakdown within cells. The study concludes that BHB holds promise as a therapeutic agent for ccRCC, targeting abnormal lipid metabolism, inducing autophagy-mediated cell death, and promoting fat browning. The results suggest potential avenues for precision-guided nutritional therapies in ccRCC treatment, highlighting the innovative role of BHB in addressing the challenges posed by this cancer.

探索β-羟丁酸(BHB)在透明细胞肾细胞癌中的治疗潜力:脂肪褐变、自噬和肿瘤瘦身之旅
这项研究深入探讨了β-羟丁酸(BHB)在透明细胞肾细胞癌(ccRCC)中的治疗潜力。这项研究特别探讨了 BHB 对 Caki-1 细胞活力、自噬诱导和脂质代谢的影响。研究结果表明,BHB 能显著降低 ccRCC 细胞的活力,尤其是在低葡萄糖条件下。葡萄糖和 BHB 联合治疗可激活自噬通路,48 小时和 72 小时后,自噬相关基因(Beclin-1、LC3IIβ 和 ATG5)的表达增加,P62 的表达减少就是证明。此外,PGC-1α和UCP-1的表达升高,以及ACSL3和CPT1A的上调都表明,联合疗法能促进脂质代谢,而ACSL3和CPT1A与脂滴的形成有关,能促进细胞内脂质的分解。研究得出结论:BHB 有望成为治疗 ccRCC 的药物,它能针对异常的脂质代谢,诱导自噬介导的细胞死亡,并促进脂肪褐变。研究结果为精确制导的营养疗法治疗 ccRCC 提供了潜在的途径,突出了 BHB 在应对这种癌症所带来的挑战方面的创新作用。
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来源期刊
CiteScore
5.30
自引率
0.00%
发文量
274
审稿时长
3-8 weeks
期刊介绍: IJCP is a general medical journal. IJCP gives special priority to work that has international appeal. IJCP publishes: Editorials. IJCP Editorials are commissioned. [Peer reviewed at the editor''s discretion] Perspectives. Most IJCP Perspectives are commissioned. Example. [Peer reviewed at the editor''s discretion] Study design and interpretation. Example. [Always peer reviewed] Original data from clinical investigations. In particular: Primary research papers from RCTs, observational studies, epidemiological studies; pre-specified sub-analyses; pooled analyses. [Always peer reviewed] Meta-analyses. [Always peer reviewed] Systematic reviews. From October 2009, special priority will be given to systematic reviews. [Always peer reviewed] Non-systematic/narrative reviews. From October 2009, reviews that are not systematic will be considered only if they include a discrete Methods section that must explicitly describe the authors'' approach. Special priority will, however, be given to systematic reviews. [Always peer reviewed] ''How to…'' papers. Example. [Always peer reviewed] Consensus statements. [Always peer reviewed] Short reports. [Always peer reviewed] Letters. [Peer reviewed at the editor''s discretion] International scope IJCP publishes work from investigators globally. Around 30% of IJCP articles list an author from the UK. Around 30% of IJCP articles list an author from the USA or Canada. Around 45% of IJCP articles list an author from a European country that is not the UK. Around 15% of articles published in IJCP list an author from a country in the Asia-Pacific region.
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