Exploring the Anticancer Properties of Cinchonine: A Comprehensive Review of Cellular and Molecular Mechanisms With Botanical Source and Pharmacokinetics Property

Cinchonine (CCN), a bioactive natural compound from Cinchona species, has gained attention for its anticancer properties. This review aims to comprehensively evaluate the mechanisms underlying CCN's anticancer activity, along with its botanical sources and pharmacokinetic (PK) properties. Therefore, data has been collected through the use of many trustworthy and well-known search tools such as PubMed, Web of Science, Google Scholar, and other reputable sources. Our findings show that CCN promotes apoptosis in a variety of cancer cell lines by upregulating reactive oxygen species (ROS), caspase-3, caspase-9, the Bcl-2-associated X protein/B-cell lymphoma-2 (Bax/Bcl-2) ratio, and poly (ADP-Ribose) polymerase (PARP) cleavage, consequently preventing the growth of different cancer cell lines. Our results also revealed that CCN exhibits anticancer effects against various cancers, including uterine sarcoma and cervical, colon, liver, lung, prostate, pancreatic, and skin cancers. These effects are mediated through multiple mechanisms, such as inducing oxidative stress, promoting cytotoxicity, and inhibiting cancer progression by suppressing cell proliferation, migration, and invasion. Additionally, it modulates critical signaling pathways such as protein kinase B (AKT) and transforming growth factor-β-activated kinase 1 (TAK1), exhibiting efficacy against multiple cancer cell lines. Moreover, CCN exhibits a promising PK profile with optimal absorption, distribution, metabolism, and excretion (ADME) characteristics in preclinical models. These findings suggested that CCN holds significant promise as a novel anticancer agent due to its multifaceted mechanisms and favorable biopharmaceutical properties. However, further clinical trials are essential to validate its safety, efficacy, and potential as a therapeutic agent for cancer treatment.