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Review
. 2024 Jul 31;25(15):8375.
doi: 10.3390/ijms25158375.

Natural Alkaloids in Cancer Therapy: Berberine, Sanguinarine and Chelerythrine against Colorectal and Gastric Cancer

Anna Duda-Madej  1 , Szymon Viscardi  2 , Wiktoria Szewczyk  2 , Ewa Topola  2
Affiliations
Review

Natural Alkaloids in Cancer Therapy: Berberine, Sanguinarine and Chelerythrine against Colorectal and Gastric Cancer

Anna Duda-Madej et al. Int J Mol Sci. .

Abstract

The rising incidence of colorectal cancer (CRC) and gastric cancer (GC) worldwide, coupled with the limited effectiveness of current chemotherapeutic agents, has prioritized the search for new therapeutic options. Natural substances, which often exhibit cytostatic properties, hold significant promise in this area. This review evaluates the anticancer properties of three natural alkaloids-berberine, sanguinarine, and chelerythrine-against CRC and GC. In vivo and in vitro studies have demonstrated that these substances can reduce tumor volume and inhibit the epithelial-mesenchymal transition (EMT) of tumors. At the molecular level, these alkaloids disrupt key signaling pathways in cancer cells, including mTOR, MAPK, EGFR, PI3K/AKT, and NF-κB. Additionally, they exhibit immunomodulatory effects, leading to the induction of programmed cell death through both apoptosis and autophagy. Notably, these substances have shown synergistic effects when combined with classical cytostatic agents such as cyclophosphamide, 5-fluorouracil, cetuximab, and erlotinib. Furthermore, berberine has demonstrated the ability to restore sensitivity in individuals originally resistant to cisplatin GC. Given these findings, natural compounds emerge as a promising option in the chemotherapy of malignant gastrointestinal tumors, particularly in cases with limited treatment options. However, more research is necessary to fully understand their therapeutic potential.

Keywords: alkaloids; anticancer; antitumor; berberine; chelerythrine; colorectal cancer; cytostatic; gastric cancer; natural compounds; sanguinarine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of berberine (A), chelerythrine (B), and sanguinarine (C).
Figure 2
Figure 2
Berberine-dependent anti-invasive impact on colorectal cancer cells (simplified scheme).
Figure 3
Figure 3
Berberine-dependent inhibition of cell cycle of colorectal cancer cells in phase G0/G1.
Figure 4
Figure 4
Berberine-dependent colorectal cancer cell apoptosis (simplified scheme).
Figure 5
Figure 5
Spectrum of molecular effects of berberine on gastric cancer cells.
See this image and copyright information in PMC

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