Isotretinoin as a Multifunctional Anticancer Agent: Molecular Mechanisms, Pharmacological Insights and Therapeutic Potential

IF 3.6 3区 医学 Q2 CHEMISTRY, MEDICINAL
Pritam Sarkar, Nasrin Sultana, Prottoy Kumar Debnath, Razina Rouf, Mohammad S. Mubarak, Shaikh Jamal Uddin, Dragoş Popa, Daniela Calina, Javad Sharifi-Rad
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引用次数: 0

Abstract

Despite notable advancements in conventional cancer therapies, challenges such as drug resistance, adverse effects, and high treatment costs remain significant obstacles. This situation calls for exploring new therapeutic options. One promising approach is drug repurposing, which uses existing medications with known effects to identify new anticancer agents. Isotretinoin (13-cis-retinoic acid), a vitamin A derivative typically used to treat severe acne, shows considerable potential as an anticancer agent. Recent studies suggest that isotretinoin has the potential to enhance the efficacy of cancer treatment and contribute to cancer inhibition by targeting specific molecular pathways. This review explores isotretinoin's chemistry, pharmacokinetics, and toxicity, emphasizing its role in cancer treatment through clinical and preclinical studies while elucidating its anticancer mechanisms. Both preclinical and clinical studies have revealed that isotretinoin can effectively inhibit the growth of tumor cells, induce apoptosis, and help regulate cellular differentiation in a range of cancers, including neuroblastoma, glioblastoma, breast, skin, lung, ovarian, cervical, and head and neck cancers. Isotretinoin works against cancer through several mechanisms. It activates retinoic acid receptors (RARs), suppresses oncogenic signaling pathways, and influences gene transcription related to cell cycle control and apoptosis. Moreover, combining isotretinoin with other treatments, like interferon-alpha, chemotherapy drugs, or other targeted inhibitors, can create synergistic effects that improve treatment effectiveness and potentially lessen side effects. Although isotretinoin holds great promise, we still need more research to address its limitations, such as its toxicity, risks during pregnancy, and differing responses in various cancer types. Current research focuses on optimizing isotretinoin-based therapies by refining dosage regimens to maximize efficacy and enhancing formulation strategies for improved absorption and reduced side effects. Ultimately, the use of isotretinoin in cancer treatment demonstrates the potential of repurposing established drugs and paves the way for more accessible and cost-effective cancer therapies.

Abstract Image

异维甲酸作为一种多功能抗癌药物:分子机制、药理研究和治疗潜力
尽管传统的癌症治疗方法取得了显著的进步,但诸如耐药性、副作用和高昂的治疗费用等挑战仍然是重大障碍。这种情况要求探索新的治疗方案。一种很有希望的方法是药物再利用,即使用已知效果的现有药物来识别新的抗癌药物。异维甲酸(13-顺式维甲酸)是一种维生素a衍生物,通常用于治疗严重的痤疮,显示出相当大的抗癌潜力。最近的研究表明,异维a酸具有提高癌症治疗效果的潜力,并通过靶向特定的分子途径促进癌症抑制。本文综述了异维甲酸的化学、药代动力学和毒性,通过临床和临床前研究强调了异维甲酸在癌症治疗中的作用,并阐明了其抗癌机制。临床前和临床研究均表明,异维甲酸在神经母细胞瘤、胶质母细胞瘤、乳腺癌、皮肤癌、肺癌、卵巢癌、宫颈癌、头颈癌等多种癌症中均能有效抑制肿瘤细胞的生长,诱导细胞凋亡,并有助于调节细胞分化。异维a酸通过几种机制抗癌。它激活视黄酸受体(RARs),抑制致癌信号通路,并影响与细胞周期控制和凋亡相关的基因转录。此外,将异维a酸与干扰素- α、化疗药物或其他靶向抑制剂等其他治疗方法联合使用,可以产生协同效应,提高治疗效果,并可能减少副作用。尽管异维甲酸具有很大的前景,但我们仍然需要更多的研究来解决它的局限性,比如它的毒性,怀孕期间的风险,以及对不同癌症类型的不同反应。目前的研究重点是通过改进剂量方案来优化基于异维甲酸的治疗,以最大限度地提高疗效,并加强配方策略,以改善吸收和减少副作用。最终,异维a酸在癌症治疗中的使用显示了重新利用现有药物的潜力,并为更容易获得和更具成本效益的癌症治疗铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Archiv der Pharmazie
Archiv der Pharmazie 医学-化学综合
CiteScore
7.90
自引率
5.90%
发文量
176
审稿时长
3.0 months
期刊介绍: Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.
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