Rubus Occidentalis and its bioactive compounds against cancer: From molecular mechanisms to translational advances

Background: Cancer ranks as the second leading cause of death globally, imposing a significant public health burden. The rise in cancer resistance to current therapeutic agents underscores the potential role of phytotherapy. Black raspberry (BRB, Rubus Occidentalis) is a fruit rich in anthocyanins, ellagic acid, and ellagitannins. Accumulating evidence suggests that BRB exhibits promising anticancer effects, positioning it as a viable candidate for phytotherapy. Purpose: This article aims to review the existing research on BRB regarding its role in cancer prevention and treatment. It further analyzes the effective components of BRB, their metabolic pathways, and the potential mechanisms underlying the fruit's anticancer effects. Methods: Ovid MEDLINE, EMBASE, Web of Science, and CENTRAL were searched through the terms of Black Raspberry, Raspberry, and Rubus Occidentali up to January 2023. Two reviewers performed the study selection by screening the title and abstract. Full texts of potentially eligible studies were retrieved to access the details. Results: Out of the 767 articles assessed, 73 papers met the inclusion criteria. Among them, 63 papers investigated the anticancer mechanisms, while 10 conducted clinical trials focusing on cancer treatment or prevention. BRB was found to influence multiple cancer hallmarks by targeting various pathways. Decomposition of free radicals and regulation of estrogen metabolism, BRB can reduce DNA damage caused by reactive oxygen species. BRB can also enhance the function of nucleotide excision repair to repair DNA lesions. Through regulation of epigenetics, BRB can enhance the expression of tumor suppressor genes, inducing cell cycle arrest, and promoting apoptosis and pyroptosis. BRB can reduce the energy and nutrients supply to the cancer nest by inhibiting glycolysis and reducing angiogenesis. The immune and inflammatory microenvironment surrounding cancer cells can also be ameliorated by BRB, inhibiting cancer initiation and progression. However, the limited bioavailability of BRB diminishes its anticancer efficacy. Notably, topical applications of BRB, such as gels and suppositories, have demonstrated significant clinical benefits. Conclusion: BRB inhibits cancer initiation, progression, and metastasis through diverse anticancer mechanisms while exhibiting minimal side effects. Given its potential, BRB emerges as a promising phototherapeutic agent for cancer treatment.