Ranjan Gaurav, Ranjan Shashi, Sunita Priyashree, Pattanayak Shakti Prasad
Department of Pharmacy, School of Health Sciences, Central University of South Bihar, Gaya, 824236, India.
Department of Surgery, Case Comprehensive Cancer Centre, Case Western Reserve University, Wolstein Research Building 2103 Cornell Rd, Cleveland, OH, 44106, USA.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May;398(5):4705-4725. doi: 10.1007/s00210-024-03661-z. Epub 2024 Dec 2.
Thiazolidinedione derivatives have shown significant potential as targeted cancer therapies by leveraging their various mechanisms of action. These include suppressing cell proliferation, triggering apoptosis, and influencing signaling pathways associated with tumor development. Their multifaceted effects make them promising candidates for advancing cancer treatment strategies. They have shown significant promise as anti-cancer agents, particularly through their ability to inhibit lipogenesis pathways and apoptosis essential for cancer cell survival and proliferation. This review comprehensively examines the anti-cancer potential of thiazolidinedione derivatives by targeting key aspects of lipid metabolism, apoptosis, and various mechanistic pathways. This review provides an in-depth examination of the anti-cancer potential of TZD derivatives, focusing on their mechanisms of action, therapeutic applications, and future directions in oncology. The anti-tumor effects of TZDs primarily involve the stimulation of peroxisome proliferator-activated receptor gamma (PPAR-γ), suppressing cell proliferation, induction of apoptosis, and inhibition of angiogenesis. Moreover, recent evidence highlights their ability to modulate non-PPAR-γ pathways, such as PI3K/Akt, NF-κB, and MAPK, further expanding their role in overcoming drug resistance and enhancing therapeutic outcomes. This review explores the preclinical (in vitro and in vivo) and clinical research investigating TZD derivatives efficacy in various cancer types. The insights underscore the significance of targeting lipogenesis as a novel anti-cancer strategy, positioning thiazolidinedione derivatives as potent candidates for future cancer therapeutics. As the oncology landscape evolves, TZD derivatives (rosiglitazone, pioglitazone, inolitazone, troglitazone, and 2,4-thiazolidinedione derivatives) represent a promising class of agents with the potential to contribute meaningfully to cancer treatment. By integrating existing knowledge with recent advancements, this study provides valuable insights into the role of thiazolidinedione derivatives in cancer treatment, paving the way for further research and clinical applications.
噻唑烷二酮衍生物通过利用其多种作用机制，已显示出作为靶向癌症疗法的巨大潜力。这些机制包括抑制细胞增殖、触发细胞凋亡以及影响与肿瘤发展相关的信号通路。它们的多方面作用使其成为推进癌症治疗策略的有希望的候选药物。作为抗癌剂，它们已显示出巨大的前景，特别是通过其抑制对癌细胞存活和增殖至关重要的脂肪生成途径和细胞凋亡的能力。本综述通过针对脂质代谢、细胞凋亡和各种机制途径的关键方面，全面研究了噻唑烷二酮衍生物的抗癌潜力。本综述深入研究了噻唑烷二酮衍生物（TZD）的抗癌潜力，重点关注其作用机制、治疗应用以及肿瘤学的未来方向。TZD的抗肿瘤作用主要涉及刺激过氧化物酶体增殖物激活受体γ（PPAR-γ）、抑制细胞增殖、诱导细胞凋亡和抑制血管生成。此外，最近的证据突出了它们调节非PPAR-γ途径（如PI3K/Akt、NF-κB和MAPK）的能力，进一步扩大了它们在克服耐药性和提高治疗效果方面的作用。本综述探讨了研究TZD衍生物在各种癌症类型中疗效的临床前（体外和体内）和临床研究。这些见解强调了将脂肪生成作为一种新型抗癌策略的重要性，将噻唑烷二酮衍生物定位为未来癌症治疗的有力候选药物。随着肿瘤学领域的发展，TZD衍生物（罗格列酮、吡格列酮、依帕列净、曲格列酮和2,4-噻唑烷二酮衍生物）代表了一类有前途的药物，有可能对癌症治疗做出有意义的贡献。通过将现有知识与最新进展相结合，本研究为噻唑烷二酮衍生物在癌症治疗中的作用提供了有价值的见解，为进一步的研究和临床应用铺平了道路。
