Background/Objectives:Ascorbic acid (AA)is a micronutrient with concentration-dependent anticancer properties, acting either as a reactive oxygen species (ROS) scavenger or inducer.Methods: Conventional redox-based assays such as MTS/MTT often overestimate cell proliferation due to AA’s interaction with tetrazolium salts, leading to increased formazan production. To overcome this limitation, we employed the Propidium Iodide Triton X-100 (PI/TX-100) assay to evaluate AA’s cytotoxic effects across a diverse panel of cancer and normal cell lines, including prostate (22Rv1, C4-2B, DU-145, LNCaP), breast (MCF-7, MDA-MB-231, MDA-MB-453), lung (A549), liver (HepG2, SK-HEP-1, Huh7), and kidney (Vero) cells.Results: AA significantly suppressed cancer cell viability compared to normal cells (RWPE1 and Vero), with the strongest effects observed in hormone receptor-positive lines. The relative sensitivity to AA followed distinct patterns within each cancer type. Mechanistically, AA-induced cell death involved ROS generation, lipid peroxidation, cell cycle arrest, ferroptosis, apoptosis, and downregulation of pyruvate dehydrogenase kinase 1 (PDHK1).Conclusions:These findings further support the potential of AA as a selective anticancer agent and highlight the importance of assay choice in evaluating its therapeutic efficacy.
背景/目的：抗坏血酸（AA）是一种具有浓度依赖性抗癌特性的微量营养素，既能作为活性氧（ROS）清除剂，也能作为诱导剂发挥作用。方法：由于抗坏血酸与四唑盐相互作用导致甲臜生成增加，MTS/MTT等传统基于氧化还原反应的检测方法往往会高估细胞增殖。为克服这一局限，我们采用碘化丙啶-曲拉通X-100（PI/TX-100）检测法，评估了抗坏血酸对多种癌细胞系和正常细胞系的细胞毒性作用，包括前列腺癌（22Rv1、C4-2B、DU-145、LNCaP）、乳腺癌（MCF-7、MDA-MB-231、MDA-MB-453）、肺癌（A549）、肝癌（HepG2、SK-HEP-1、Huh7）及肾细胞（Vero）。结果：与正常细胞（RWPE1和Vero）相比，抗坏血酸显著抑制癌细胞活力，其中对激素受体阳性细胞系的作用最为明显。在不同癌症类型中，细胞对抗坏血酸的相对敏感性呈现特定规律。机制研究表明，抗坏血酸诱导的细胞死亡涉及ROS生成、脂质过氧化、细胞周期阻滞、铁死亡、细胞凋亡以及丙酮酸脱氢酶激酶1（PDHK1）的下调。结论：这些发现进一步支持了抗坏血酸作为选择性抗癌剂的潜力，并强调了检测方法选择对其疗效评估的重要性。
肿瘤(癌症)患者之家