Saha Tushara, Banerjee Srijoni, Priya Kanu, Giri Shiv Kumar, Rajeev Mithul, Singh Shareen, Rustagi Sarvesh, Bhattacharya Debasmita, Nag Moupriya, Gill Harjot Singh, Lahiri Dibyajit
Department of Biotechnology, SOLB, Adamas University, Kolkata, 700126, India.
Centre for Phytochemical Research, Department of Life Science, School of Basic Science and Research, Sharda University, Greater Noida, U.P, India.
Med Oncol. 2025 Sep 10;42(11):467. doi: 10.1007/s12032-025-02992-y.
Oligomeric proanthocyanidins (OPCs), condensed tannins found plentiful in grape seeds and berries, have higher bioavailability and therapeutic benefits due to their low degree of polymerization. Recent evidence places OPCs as effective modulators of cancer stem cell (CSC) plasticity and tumor growth. Mechanistically, OPCs orchestrate multi-pathway inhibition by destabilizing Wnt/β-catenin, Notch, PI3K/Akt/mTOR, JAK/STAT3, and Hedgehog pathways, triggering β-catenin degradation, silencing stemness regulators (OCT4, NANOG, SOX2), and stimulating tumor-suppressive microRNAs (miR-200, miR-34a). Furthermore, OPCs reorganize the tumor microenvironment by suppressing CSC markers (CD44, CD133, ALDH1, EpCAM) and reconstituting immune surveillance. Preclinical in-vitro and in-vivo models in colorectal, breast, and prostate cancers show OPC-mediated CSC elimination, apoptosis, and chemosensitization with minimal systemic toxicity. Emerging advances-redox-sensitive and pH-sensitive nanocarriers, exosome-based delivery, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 functional screens, and patient-derived organoids-present revolutionary solutions to overcome bioavailability bottlenecks and deliver precision-targeted therapies. These advances highlight the promise of OPCs as next-generation, multi-targeted anti-CSC oncology therapeutics.
低聚原花青素（OPCs）是在葡萄籽和浆果中大量存在的缩合单宁，由于其低聚合度而具有更高的生物利用度和治疗益处。最近的证据表明，OPCs是癌症干细胞（CSC）可塑性和肿瘤生长的有效调节剂。从机制上讲，OPCs通过破坏Wnt/β-连环蛋白、Notch、PI3K/Akt/mTOR、JAK/STAT3和Hedgehog信号通路来协调多途径抑制，触发β-连环蛋白降解，使干性调节因子（OCT4、NANOG、SOX2）沉默，并刺激肿瘤抑制性微小RNA（miR-200、miR-34a）。此外，OPCs通过抑制CSC标志物（CD44、CD133、ALDH1、EpCAM）和重建免疫监视来重组肿瘤微环境。结直肠癌、乳腺癌和前列腺癌的临床前体外和体内模型显示，OPCs介导的CSC消除、细胞凋亡和化学增敏作用，全身毒性最小。新出现的进展——氧化还原敏感和pH敏感的纳米载体、基于外泌体的递送、成簇规律间隔短回文重复序列（CRISPR）-Cas9功能筛选以及患者来源的类器官——为克服生物利用度瓶颈和提供精准靶向治疗提供了革命性的解决方案。这些进展凸显了OPCs作为下一代多靶点抗CSC肿瘤治疗药物的前景。
