Alkaloids in Cancer therapy: Targeting the tumor microenvironment and metastasis signaling pathways

The use of phytomedicine in cancer therapy is a growing field of research that takes use of the medicinal properties of plant-derived compounds. Under the domain of cancer therapy and management, alkaloids, a prominent group of natural compounds, have showed significant potential. Alkaloids often affect a wide range of essential cellular mechanisms involved in cancer progression. These multi-targeting capabilities, can give significant advantages to alkaloids in overcoming resistance mechanisms. For example, berberine, an alkaloid found in Berberis species, is widely reported to induce apoptosis by activating caspases and regulating apoptotic pathways. Notably, alkaloids like as quinine have showed promise in inhibiting the formation of new blood vessels required for tumor growth. In addition, alkaloids have shown anti-proliferative and anticancer properties mostly via modulating key signaling pathways involved in metastasis, including those regulating epithelial-mesenchymal transition. This work provides a comprehensive overview of naturally occurring alkaloids that exhibit anticancer properties, with a specific emphasis on their underlying molecular mechanisms of action. Furthermore, many methods to modify previously reported difficult physicochemical properties using nanocarriers in order to enhance its systemic bioavailability have been discussed as well. This study also includes information on newly discovered alkaloids that are now being studied in clinical trials for their potential use in cancer treatment. Further, we have also briefly mentioned on the application of high-throughput screening and molecular dynamics simulation for acceleration on the identification of potent alkaloids based compounds to target and treat cancer.