Debnath Ishita, Kundu Moumita
Guru Nanak Institute of Pharmaceutical Science and Technology, Kolkata, India.
Center for Multidisciplinary Research & Innovations, Brainware University, Kolkata, West Bengal, India.
Discov Oncol. 2025 Jul 28;16(1):1433. doi: 10.1007/s12672-025-03190-y.
Cancer stem cells (CSCs) are a specific subset of cancer cells that possess the ability to self-renew, resist therapies, and promote metastasis, making them a crucial target in cancer treatment. This study investigates the therapeutic potential of natural compounds in targeting CSCs, particularly their ability to inhibit key signaling pathways, induce apoptosis, and alter the tumor microenvironment. This article reviews the molecular mechanisms that maintain CSCs and contribute to their resistance, focusing on the roles of the WNT/β-catenin, Hedgehog, Notch, and PI3K/ATK/mTOR pathways. Several natural compounds, including curcumin, resveratrol, epigallocatechin gallate, and sulforaphane, were assessed for their effectiveness in targeting CSCs. The finding revealed that these natural compounds can inhibit CSC proliferation, enhance sensitivity to chemotherapy, and suppress the tumor-supportive microenvironment. Notably, compounds such as berberine and piperine were found to reverse drug resistance by downregulating efflux transporters, while quercetin and salinomycin selectively induced apoptosis in CSCs. Overall, natural compounds show promising potential for targeting CSCs in therapy. However, challenges related to bioavailability and metabolic stability must be addressed through advanced drug delivery systems and combination therapy.
癌症干细胞（CSCs）是癌细胞的一个特定亚群，具有自我更新、抵抗治疗和促进转移的能力，使其成为癌症治疗中的关键靶点。本研究调查了天然化合物在靶向癌症干细胞方面的治疗潜力，特别是它们抑制关键信号通路、诱导细胞凋亡和改变肿瘤微环境的能力。本文综述了维持癌症干细胞并导致其耐药性的分子机制，重点关注WNT/β-连环蛋白、Hedgehog、Notch和PI3K/ATK/mTOR信号通路的作用。评估了几种天然化合物，包括姜黄素、白藜芦醇、表没食子儿茶素没食子酸酯和萝卜硫素，在靶向癌症干细胞方面的有效性。研究结果表明，这些天然化合物可以抑制癌症干细胞增殖，增强对化疗的敏感性，并抑制肿瘤支持性微环境。值得注意的是，黄连素和胡椒碱等化合物被发现通过下调外排转运蛋白来逆转耐药性，而槲皮素和沙利霉素则选择性地诱导癌症干细胞凋亡。总体而言，天然化合物在治疗中靶向癌症干细胞显示出有前景的潜力。然而，与生物利用度和代谢稳定性相关的挑战必须通过先进的药物递送系统和联合治疗来解决。
