Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy.
Ralph N. Adams Institute for Bioanalytical Chemistry, University of Kansas, Lawrence, KS 66047, USA.
Cells. 2023 Nov 8;12(22):2592. doi: 10.3390/cells12222592.
Carnosine is an endogenous dipeptide composed of β-alanine and L-histidine, possessing a multimodal pharmacodynamic profile that includes anti-inflammatory and anti-oxidant activities. Carnosine has also shown its ability to modulate cell proliferation, cell cycle arrest, apoptosis, and even glycolytic energy metabolism, all processes playing a key role in the context of cancer. Cancer is one of the most dreaded diseases of the 20th and 21st centuries. Among the different types of cancer, breast cancer represents the most common non-skin cancer among women, accounting for an estimated 15% of all cancer-related deaths in women. The main aim of the present review was to provide an overview of studies on the anti-cancer activity of carnosine, and in particular its activity against breast cancer. We also highlighted the possible advantages and limitations involved in the use of this dipeptide. The first part of the review entailed a brief description of carnosine's biological activities and the pathophysiology of cancer, with a focus on breast cancer. The second part of the review described the anti-tumoral activity of carnosine, for which numerous studies have been carried out, especially at the preclinical level, showing promising results. However, only a few studies have investigated the therapeutic potential of this dipeptide for breast cancer prevention or treatment. In this context, carnosine has shown to be able to decrease the size of cancer cells and their viability. It also reduces the levels of vascular endothelial growth factor (VEGF), cyclin D1, NAD, and ATP, as well as cytochrome c oxidase activity in vitro. When tested in mice with induced breast cancer, carnosine proved to be non-toxic to healthy cells and exhibited chemopreventive activity by reducing tumor growth. Some evidence has also been reported at the clinical level. A randomized phase III prospective placebo-controlled trial showed the ability of Zn-carnosine to prevent dysphagia in breast cancer patients undergoing adjuvant radiotherapy. Despite this evidence, more preclinical and clinical studies are needed to better understand carnosine's anti-tumoral activity, especially in the context of breast cancer.
肌肽是由β-丙氨酸和 L-组氨酸组成的内源性二肽,具有多模式的药效学特征,包括抗炎和抗氧化活性。肌肽还显示出调节细胞增殖、细胞周期停滞、细胞凋亡,甚至糖酵解能量代谢的能力,所有这些过程在癌症中都起着关键作用。癌症是 20 世纪和 21 世纪最可怕的疾病之一。在不同类型的癌症中,乳腺癌是女性最常见的非皮肤癌,估计占女性所有癌症相关死亡人数的 15%。本综述的主要目的是提供对肌肽抗癌活性的研究概述,特别是其对乳腺癌的活性。我们还强调了使用这种二肽可能涉及的优势和局限性。综述的第一部分简要描述了肌肽的生物学活性和癌症的病理生理学,重点是乳腺癌。综述的第二部分描述了肌肽的抗肿瘤活性,已经进行了大量研究,特别是在临床前水平,显示出有希望的结果。然而,只有少数研究调查了这种二肽预防或治疗乳腺癌的治疗潜力。在这种情况下,肌肽已被证明能够减小癌细胞的大小及其活力。它还降低了血管内皮生长因子 (VEGF)、细胞周期蛋白 D1、NAD 和 ATP 的水平,以及体外细胞色素 c 氧化酶的活性。在诱导乳腺癌的小鼠中进行测试时,肌肽被证明对健康细胞无毒,并且通过减少肿瘤生长表现出化学预防活性。在临床水平也有一些证据报道。一项随机 III 期前瞻性安慰剂对照试验表明,Zn-肌肽能够预防接受辅助放疗的乳腺癌患者发生吞咽困难。尽管有这些证据,但仍需要更多的临床前和临床研究来更好地了解肌肽的抗肿瘤活性,特别是在乳腺癌方面。