Wong Shu Chyi, Kamarudin Muhamad Noor Alfarizal, Naidu Rakesh
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia.
Brain Research Institute Monash Sunway (BRIMS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia.
Nutrients. 2021 Mar 16;13(3):950. doi: 10.3390/nu13030950.
Glioblastoma (GBM) is the most malignant brain tumor and accounts for most adult brain tumors. Current available treatment options for GBM are multimodal, which include surgical resection, radiation, and chemotherapy. Despite the significant advances in diagnostic and therapeutic approaches, GBM remains largely resistant to treatment, with a poor median survival rate between 12 and 18 months. With increasing drug resistance, the introduction of phytochemicals into current GBM treatment has become a potential strategy to combat GBM. Phytochemicals possess multifarious bioactivities with multitarget sites and comparatively marginal toxicity. Among them, curcumin is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways properties. Curcumin possesses the ability to modulate the core pathways involved in GBM cell proliferation, apoptosis, cell cycle arrest, autophagy, paraptosis, oxidative stress, and tumor cell motility. This review discusses curcumin's anticancer mechanism through modulation of Rb, p53, MAPK, P13K/Akt, JAK/STAT, Shh, and NF-κB pathways, which are commonly involved and dysregulated in preclinical and clinical GBM models. In addition, limitation issues such as bioavailability, pharmacokinetics perspectives strategies, and clinical trials were discussed.
胶质母细胞瘤(GBM)是最恶性的脑肿瘤,占大多数成人脑肿瘤。目前GBM可用的治疗方案是多模式的,包括手术切除、放疗和化疗。尽管在诊断和治疗方法上取得了重大进展,但GBM对治疗仍具有很大的抗性,中位生存率低,在12至18个月之间。随着耐药性的增加,将植物化学物质引入当前的GBM治疗已成为对抗GBM的一种潜在策略。植物化学物质具有多种生物活性、多靶点作用且毒性相对较小。其中,姜黄素是研究最多的化合物,由于其多靶点信号/分子途径特性而被描述为一种潜在的抗癌剂。姜黄素具有调节GBM细胞增殖、凋亡、细胞周期停滞、自噬、副凋亡、氧化应激和肿瘤细胞运动等核心途径的能力。本综述讨论了姜黄素通过调节Rb、p53、MAPK、P13K/Akt、JAK/STAT、Shh和NF-κB途径的抗癌机制,这些途径在临床前和临床GBM模型中通常涉及且失调。此外,还讨论了生物利用度、药代动力学观点策略和临床试验等局限性问题。