Raghavendra Institute of Pharmaceutical Education and Research, Anantapur, India.
Department of Pharmacology, Balaji College of Pharmacy, Anantapur, India.
Front Endocrinol (Lausanne). 2023 Jul 25;14:1201198. doi: 10.3389/fendo.2023.1201198. eCollection 2023.
Colorectal cancer (CRC) is one of the most deaths causing diseases worldwide. Several risk factors including hormones like insulin and insulin like growth factors (e.g., IGF-1) have been considered responsible for growth and progression of colon cancer. Though there is a huge advancement in the available screening as well as treatment techniques for CRC. There is no significant decrease in the mortality of cancer patients. Moreover, the current treatment approaches for CRC are associated with serious challenges like drug resistance and cancer re-growth. Given the severity of the disease, there is an urgent need for novel therapeutic agents with ideal characteristics. Several pieces of evidence suggested that natural products, specifically medicinal plants, and derived phytochemicals may serve as potential sources for novel drug discovery for various diseases including cancer. On the other hand, cancer cells like colon cancer require a high basal level of reactive oxygen species (ROS) to maintain its own cellular functions. However, excess production of intracellular ROS leads to cancer cell death disturbing cellular redox homeostasis. Therefore, medicinal plants and derived phytocompounds that can enhance the intracellular ROS and induce apoptotic cell death in cancer cells modulating various molecular targets including IGF-1 could be potential therapeutic agents. Alkaloids form a major class of such phytoconstituents that can play a key role in cancer prevention. Moreover, several preclinical and clinical studies have also evidenced that these compounds show potent anti-colon cancer effects and exhibit negligible toxicity towards the normal cells. Hence, the present evidence-based study aimed to provide an update on various alkaloids that have been reported to induce ROS-mediated apoptosis in colon cancer cells targeting various cellular components including hormones and growth factors, which play a role in metastasis, angiogenesis, proliferation, and invasion. This study also provides an individual account on each such alkaloid that underwent clinical trials either alone or in combination with other clinical drugs. In addition, various classes of phytochemicals that induce ROS-mediated cell death in different kinds of cancers including colon cancer are discussed.
结直肠癌（CRC）是全球导致死亡的主要疾病之一。一些风险因素，如胰岛素和胰岛素样生长因子（例如 IGF-1）等激素，被认为是导致结肠癌生长和进展的原因。尽管在 CRC 的现有筛查和治疗技术方面取得了巨大进展，但癌症患者的死亡率并没有显著下降。此外，CRC 的当前治疗方法存在严重挑战，如耐药性和癌症复发。鉴于该疾病的严重性，迫切需要具有理想特性的新型治疗剂。有几项证据表明，天然产物，特别是药用植物和衍生的植物化学物质，可能成为包括癌症在内的各种疾病的新型药物发现的潜在来源。另一方面，癌细胞（如结肠癌）需要高水平的活性氧（ROS）来维持其自身的细胞功能。然而，过多的细胞内 ROS 产生会导致癌细胞死亡，扰乱细胞的氧化还原平衡。因此，能够增强细胞内 ROS 并诱导癌细胞凋亡的药用植物和衍生的植物化合物，通过调节 IGF-1 等各种分子靶标，可能成为潜在的治疗剂。生物碱是此类植物成分的主要类别之一，可在癌症预防中发挥关键作用。此外，一些临床前和临床研究也证明，这些化合物对结肠癌具有很强的抑制作用，对正常细胞几乎没有毒性。因此，本基于证据的研究旨在提供各种生物碱的最新信息，这些生物碱已被报道可诱导 ROS 介导的结肠癌细胞凋亡，针对包括激素和生长因子在内的各种细胞成分，这些成分在转移、血管生成、增殖和侵袭中发挥作用。本研究还分别介绍了每种生物碱的情况，这些生物碱单独或与其他临床药物联合进行了临床试验。此外，还讨论了可诱导不同类型癌症（包括结肠癌）中 ROS 介导的细胞死亡的各种植物化学物质。
