INTERNATIONAL CONGRESS OF
PharmacoGenetics
Unlocking Nature's Arsenal: The Expanding Therapeutic Role of Berberine in Combating Lung Cancer
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Hamed Mirzaei,1 Farzaneh Davtalab,2,*
1. Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
2. Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Introduction: Lung cancer remains the most formidable adversary in the field of oncology, distinguished by its high incidence and its status as the leading cause of cancer-related mortality worldwide. The complexity of its etiology is not yet fully understood; while tobacco smoke is the primary driver, a substantial number of cases arise from other risk factors, including occupational exposure to carcinogens, ambient air pollution, and genetic predispositions. Current standard-of-care treatments, such as chemotherapy, radiation, and even targeted therapies, are often hampered by significant side effects and the eventual development of treatment resistance. This clinical reality creates an urgent and persistent need for novel therapeutic agents that can effectively target the disease through different mechanisms, ideally with a more favorable safety profile. In this context, natural compounds have emerged as a rich source of potential anti-cancer agents. Among them, berberine, an isoquinoline alkaloid extracted from plants like Goldenseal and Berberis species, has garnered considerable scientific attention. Long used in traditional medicine, its modern pharmacological profile is remarkably broad, with validated anti-hyperglycemic, anti-inflammatory, anti-oxidative, and potent anti-cancer properties. Emerging evidence strongly suggests that berberine exerts its anti-tumor effects by systematically targeting a multitude of cellular and molecular processes. This review, therefore, undertakes a comprehensive synthesis of the existing literature to illuminate the precise pathways that berberine modulates in its fight against lung cancer cells. Methodology: A Systematic Review of the Evidence To construct this overview, a rigorous and systematic literature search was meticulously conducted. The researchers queried leading biomedical databases, including MEDLINE, EMBASE, and Web of Science, to identify all relevant studies. The search encompassed all publications indexed up to September 30, 2024, using the keywords "berberine" and "lung cancer" to ensure a focused and relevant collection of data.
- Methods: To construct this overview, a rigorous and systematic literature search was meticulously conducted. The researchers queried leading biomedical databases, including MEDLINE, EMBASE, and Web of Science, to identify all relevant studies. The search encompassed all publications indexed up to September 30, 2024, using the keywords "berberine" and "lung cancer" to ensure a focused and relevant collection of data.
- Results: The synthesized research reveals that berberine combats lung cancer through several distinct but interconnected mechanisms. Its primary anti-cancer effect is the potent induction of programmed cell death (apoptosis). It achieves this by strategically altering the balance of key regulatory proteins, activating pro-apoptotic molecules like Bax, Bak, cytochrome−c, and the final executioner enzyme, caspase−3. Concurrently, it suppresses the expression of pro- survival proteins such as Bcl−2 and Bcl−xl, effectively dismantling the cancer cells' defenses against self-destruction. This apoptotic cascade is driven by berberine's ability to disrupt critical survival signaling pathways, including the PI3K/AKT, Raf/MEK/ERK, and p53 networks. Beyond inducing cell death, berberine actively halts the uncontrolled proliferation of lung cancer cells by inducing cell-cycle arrest, primarily in the G0/G1 phase. This action prevents the cells from proceeding to the DNA synthesis (S) phase, thereby stopping tumor growth at its source. Furthermore, berberine directly counteracts the high metastatic potential that makes lung cancer so deadly. It has been shown to cripple the cancer cells' ability to migrate and invade new tissues by downregulating key targets such as matrix metalloproteinase-2 (MMP2), urokinase-type plasminogen activator (u−PA), and transcription factors c−Jun and c−Fos. It also disrupts inflammatory and angiogenic (new blood vessel formation) signaling, most notably by inhibiting the NF−κB/COX−2 pathway and the critical HIF−1α/VEGF axis, which tumors use to build their own blood supply.
- Conclusion: The compiled evidence strongly positions berberine as a highly promising agent for integration into lung cancer treatment protocols. Its ability to simultaneously induce apoptosis, arrest the cell cycle, and inhibit metastasis suggests it could serve as a powerful complementary therapy to enhance the efficacy of conventional treatments or perhaps as an alternative therapeutic for specific patient groups. However, the translation from preclinical findings to clinical practice requires further rigorous investigation. Future efforts must prioritize well-designed clinical trials to establish its safety, optimal dosage, and definitive efficacy in patients. Continued molecular research is also vital to fully delineate the intricate pathways it influences and to identify potential biomarkers that could predict patient response, paving the way for a more personalized and effective application of this potent natural compound.
- Keywords: Berberine Lung Cancer Apoptosis Cell Cycle Arrest Metastasis Inhibition
