Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy.
Research Institute on Terrestrial Ecosystems (IRET), UOS Naples-Consiglio Nazionale delle Ricerche (CNR), Via Pietro Castellino 111, 80131 Naples, Italy.
Int J Mol Sci. 2022 Jul 30;23(15):8464. doi: 10.3390/ijms23158464.
Recent pharmacological research on milk whey, a byproduct of the dairy industry, has identified several therapeutic properties that could be exploited in modern medicine. In the present study, we investigated the anticancer effects of whey from Mediterranean buffalo () milk. The antitumour effect of delactosed milk whey (DMW) was evaluated using the HCT116 xenograft mouse model of colorectal cancer (CRC). There were no discernible differences in tumour growth between treated and untreated groups. Nevertheless, haematoxylin and eosin staining of the xenograft tissues showed clearer signs of different cell death in DMW-treated mice compared to vehicle-treated mice. Detailed biochemical and molecular biological analyses revealed that DMW was able to downregulate the protein expression levels of c-myc, phospho-Histone H3 (ser 10) and p-ERK. Moreover, DMW also activated RIPK1, RIPK3, and MLKL axis in tumour tissues from xenograft mice, thus, suggesting a necroptotic effect. The necroptotic pathway was accompanied by activation of the apoptotic pathway as revealed by increased expression of both cleaved caspase-3 and PARP-1. At the molecular level, DMW-induced cell death was also associated with (i) upregulation of SIRT3, SIRT6, and PPAR-γ and (ii) downregulation of LDHA and PPAR-α. Overall, our results unveil the potential of whey as a source of biomolecules of food origin in the clinical setting of novel strategies for the treatment of CRC.
最近对乳清（乳制品工业的副产品）的药理学研究发现了其几种可能在现代医学中应用的治疗特性。在本研究中，我们研究了来自地中海水牛（）奶的乳清的抗癌作用。使用结直肠癌细胞（CRC）的 HCT116 异种移植小鼠模型评估了去乳糖乳清（DMW）的抗肿瘤作用。在治疗组和未治疗组之间，肿瘤生长没有明显差异。然而，与未处理组相比，DMW 处理组的异种移植组织的苏木精和伊红染色显示出更明显的不同细胞死亡迹象。详细的生化和分子生物学分析表明，DMW 能够下调 c-myc、磷酸化组蛋白 H3（ser10）和 p-ERK 的蛋白表达水平。此外，DMW 还能在异种移植小鼠的肿瘤组织中激活 RIPK1、RIPK3 和 MLKL 轴，提示发生了坏死性凋亡。坏死性凋亡途径伴随着凋亡途径的激活，表现为 cleaved caspase-3 和 PARP-1 的表达增加。在分子水平上，DMW 诱导的细胞死亡还与（i）SIRT3、SIRT6 和 PPAR-γ 的上调和（ii）LDHA 和 PPAR-α 的下调有关。总的来说，我们的研究结果揭示了乳清作为临床应用中治疗 CRC 的新型策略的生物分子来源的潜力。
