自噬是一种进化保守的过程，对于维持细胞稳态至关重要。最近，人们提出了植物化合物等自噬诱导剂在抗癌方面的潜力。在仙人掌果实中发现的二甲基苋红素是一种菜蔘素类色素，在结直肠癌细胞中具有抑制增殖和促进凋亡的活性，并与选择性甲基化沉默致癌压制基因的表观遗传变化相关。本研究证明，二甲基苋红素诱导了Caco-2细胞中自噬标志物LC3-II和Beclin1的上调表达，并增加了自噬溶酶体的生成。甲基组学研究表明，二甲基苋红素诱导的前自噬活性与表观遗传变化相关。除了在基因组水平上作为高甲基化剂的作用外，二甲基苋红素还在47个与自噬相关的基因中引起了39个显著的差异甲基化，尤其是在自噬的后期阶段所涉及的基因。此外，体外分子模拟研究表明，二甲基苋红素与Bcl-2之间有直接相互作用，进而影响了关键的自噬调控因子Beclin1的功能。外部因子，包括食物成分，可以调节癌细胞的表观遗传特征。本研究首次证明了二甲基苋红素在人结直肠癌细胞中的潜在的前自噬活性与表观遗传变化相关，并有助于勾勒其在胃肠道病理生理学中的潜在健康效应。

Autophagy is an evolutionarily conserved process critical in maintaining cellular homeostasis. Recently, the anticancer potential of autophagy inducers, including phytochemicals, was suggested. Indicaxanthin is a betalain pigment found in prickly pear fruit with antiproliferative and pro-apoptotic activities in colorectal cancer cells associated with epigenetic changes in selected methylation-silenced oncosuppressor genes. Here, we demonstrate that indicaxanthin induces the up-regulation of the autophagic markers LC3-II and Beclin1, and increases autophagolysosome production in Caco-2 cells. Methylomic studies showed that the indicaxanthin-induced pro-autophagic activity was associated with epigenetic changes. In addition to acting as a hypermethylating agent at the genomic level, indicaxanthin also induced significant differential methylation in 39 out of 47 autophagy-related genes, particularly those involved in the late stages of autophagy. Furthermore, in silico molecular modelling studies suggested a direct interaction of indicaxanthin with Bcl-2, which, in turn, influenced the function of Beclin1, a key autophagy regulator. External effectors, including food components, may modulate the epigenetic signature of cancer cells. This study demonstrates, for the first time, the pro-autophagic potential of indicaxanthin in human colorectal cancer cells associated with epigenetic changes and contributes to outlining its potential healthy effect in the pathophysiology of the gastrointestinal tract.