Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, Kerala, India.
Department of Chemistry, Wayne State University, Detroit, MI, USA.
J Food Biochem. 2021 Jul;45(7):e13761. doi: 10.1111/jfbc.13761. Epub 2021 May 24.
Chemopreventive approaches with food-derived phytochemicals are progressively rising as a significant aspect of tumor management and control. Herein, we have showcased the major phytoconstituents belonging to the group of flavanoid, as anti-cancer agents used for the treatment and prevention of hepatocellular carcinoma (HCC). Sorafenib is the sole drug used for the treatment of advanced HCC, but its clinical application is limited because of its severe adverse effects and drug resistance. Diet-based chemoprevention seems to be the way forward for this disease of malignant nature. As HCC is derived from a chronic inflammatory milieu, the regular incorporation of bioactive phytochemicals in the diet will confer protection and prevent progression to hepatocarcinogenesis. Many preclinical studies proved that the health benefits of flavonoids confer cytotoxic potential against various types of cancers including hepatocellular carcinoma. As flavonoids with excellent safety profile are abundantly present in common vegetables and fruits, they can be better utilized for chemoprevention and chemosensitization in such chronic condition. This review highlights the plausible role of the eight most promising flavonoids (Curcumin, Kaempferol, Resveratrol, Quercetin, Silibinin, Baicalein, Galangin and Luteolin) as key orchestrators of chemoprevention in hepatocellular carcinoma with preclinical and clinical evidence. An attempt to address the challenges in its clinical translation is also included. This review also provides an insight into the close association of HCC and metabolic disorders which may further decipher the chemopreventive effect of dietary bioactive from a proof of concept to extensive clinical translation. PRACTICAL APPLICATIONS: According to GLOBOCAN 2020 database, it is estimated that 905,677 new cases of liver cancer and approximately 830,180 deaths related to that. The cancer incidence and mortality are almost similar as it is diagnosed at an advanced stage in patients where systemic drug therapy is the sole approach. Due to the emergence of multidrug resistance and drug-related toxicities, most of the patient can not adhere to the therapy regimen. Flavonoids are known to be a potential anticancer agent with an excellent safety profile. These are found to be effective preclinically against hepatocellular carcinoma through modulation of numerous pathways in hepatocarcinogenesis. But, the bioavailability issue, lack of well designed-validated clinical evidence, the possibility of food-drug interaction etc limit its clinical utility. The research inputs mainly to overcome pharmacokinetic issues along with suitable validation of efficacy and toxicity will be a critical point for establishing flavonoids as an effective, safe, affordable therapeutics.
以食物来源的植物化学物质为基础的化学预防方法作为肿瘤管理和控制的一个重要方面，逐渐受到重视。在此，我们展示了属于类黄酮组的主要植物化学成分，作为用于治疗和预防肝细胞癌 (HCC) 的抗癌剂。索拉非尼是唯一用于治疗晚期 HCC 的药物，但由于其严重的不良反应和耐药性，其临床应用受到限制。基于饮食的化学预防似乎是这种恶性疾病的前进方向。由于 HCC 源自慢性炎症环境，因此将生物活性植物化学物质常规纳入饮食中，将提供保护并防止向肝癌发生发展。许多临床前研究证明，类黄酮的健康益处赋予了针对包括肝细胞癌在内的各种类型癌症的细胞毒性潜力。由于具有良好安全性的类黄酮在常见的蔬菜和水果中大量存在，因此它们可以更好地用于此类慢性疾病的化学预防和化学增敏。本综述强调了八种最有前途的类黄酮（姜黄素、山奈酚、白藜芦醇、槲皮素、水飞蓟素、黄芩素、高良姜素和木犀草素）作为 HCC 化学预防的关键协调因子的合理作用，这些作用有临床前和临床证据支持。还试图解决其临床转化中的挑战。本综述还深入探讨了 HCC 与代谢紊乱之间的密切关联，这可能从概念验证到广泛的临床转化进一步解释饮食生物活性物质的化学预防作用。实际应用：根据 GLOBOCAN 2020 数据库估计，全球每年有 905677 例新的肝癌病例和约 830180 例与肝癌相关的死亡病例。由于在患者中诊断为晚期，系统药物治疗是唯一的方法，因此癌症的发病率和死亡率几乎相同。由于出现多药耐药性和与药物相关的毒性，大多数患者无法坚持治疗方案。类黄酮作为一种具有良好安全性的潜在抗癌药物而闻名。这些在临床前研究中被证明对肝细胞癌有效，通过调节肝癌发生过程中的许多途径。但是，生物利用度问题、缺乏良好设计的验证临床证据、食物-药物相互作用的可能性等限制了其临床应用。研究投入主要集中在克服药代动力学问题，同时适当验证疗效和毒性，这将是将类黄酮确立为有效、安全、负担得起的治疗方法的关键。
