Therapeutic Potential of Alkaloids to Combat Breast Cancer: A Mechanistic Overview

Breast cancer remains a major global health concern, ranking among the leading causes of illness and mortality in women worldwide. Despite the effectiveness of conventional treatments such as surgery, chemotherapy (CT), endocrine therapy (ET), radiation therapy (RT), and targeted therapies, these approaches often fall short in providing a cure for advanced-stage patients and frequently result in adverse side effects. This limitation drives the ongoing search for therapeutic natural compounds with minimal or no side effects. Alkaloids, in particular, have garnered attention for their broad spectrum of therapeutic properties against various malignancies, including breast cancer. The objective of this review is to systematically evaluate the therapeutic potential of 14 selected alkaloids that have been tested in in vitro and some in vivo models of breast cancer along by focusing on their mechanistic actions targeting key molecular signaling pathways involved in breast cancer progression. Majorly, the capability of alkaloids to induce cell cycle arrest, pro-apoptotic mechanisms via modulating various molecular signaling pathways were discussed. Notably, pathways such as the intrinsic and extrinsic mitochondrial apoptotic pathways, PI3K/AKT/mTOR, RAS/RAF/MEK/MAPK, Wnt/β-catenin, and NF-κB cascades were highlighted. Insights into conclusion the isoquinoline and indole derivatives, particularly berberine, piperine, capsaicin, matrine, and harmine, have demonstrated significant potential effects and these compounds also exhibited the ability to overcome drug resistance, and shown synergistic effects with conventional therapies. Finally, this comprehensive review could provide an overall insight into the application of these alkaloid compounds towards the prevention of breast cancer and a foundation for future studies aimed at improving their clinical effectiveness, offering valuable prospects.