Lamellarin I: A Potential Drug for Overcoming Multidrug Resistance in Cancer

Multidrug resistance (MDR), which is linked to the overexpression of ATP binding cassette (ABC) transporters like P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated proteins (MRPs), poses a significant barrier to cancer chemotherapy. Remarkably, several lamellarins exhibit equivalent toxicity to MDR and their corresponding parental cell lines. At non-toxic concentrations, lamellarin I (9) substantially augments the cytotoxicity of doxorubicin, vinblastine, and daunorubicin in MDR cells, demonstrating a 9- to 16-fold higher potency than verapamil. Additionally, lamellarin I (9) not only elevates the intracellular concentration of rhodamine 123 in P-gp-positive LoVo/Dx cells treated with the dye in a dose-dependent manner but also increases it to levels observed in sensitive parental cells at 10μM. These findings suggest that lamellarin I (9) reverses MDR by directly inhibiting P-gp-mediated drug efflux.