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Author Spotlight: Establishing a Murine Non-Small Cell Lung Cancer Model for Developing Nanoformulations of Anticancer Drugs
Published on: May 10, 2024
Synthesis, characterization and biological activity of methotrexate-derived salts in lung cancer cells
Dário Silva1,2,3, Sandra Cordeiro2,3, Pedro V Baptista2,3
1LAQV-REQUIMTE, Nova School of Science and Technology, NOVA University Lisbon 2829-516 Caparica Portugal l.branco@fct.unl.pt.
Abstract:
Lung cancer is one of the deadliest types of cancer, and is a public health problem worldwide. Methotrexate (MTX), a class IV drug in the biopharmaceutical classification system, is a folate antagonist that has demonstrated efficacy in cancer treatment. A suitable combination of MTX as a di-anion and biocompatible counter ions allowed the modulation of their physicochemical properties. In this work, twelve MTX salts were prepared and characterized by 1H NMR, 13C NMR, and elemental analysis. The antiproliferative effects of MTX salts were studied in A459 and H1975 (lung cancer cell lines) with three promising results: [C12mim]2[MTX] (IC50 = 0.55 ± 0.25) > [C10-3-picoline]2[MTX] (IC50 = 0.94 ± 0.03) > [C10mim]2[MTX] (IC50 = 1.71 ± 0.23) in A549. These three MTX salts also demonstrated intrinsic apoptosis, avoiding necrosis and the formation of reactive oxygen species.
Insights
New methotrexate (MTX) salts show potent antiproliferative effects against lung cancer cells. These novel formulations induce apoptosis, offering a promising avenue for cancer treatment development.
Area of Science:
- Oncology
- Pharmaceutical Chemistry
Background:
- Lung cancer remains a significant global health challenge.
- Methotrexate (MTX), a folate antagonist, is an established chemotherapy agent.
- Modulating MTX physicochemical properties through salt formation can enhance its efficacy.
Purpose of the Study:
- To synthesize and characterize novel methotrexate (MTX) salts.
- To evaluate the antiproliferative activity of these MTX salts against lung cancer cell lines.
- To investigate the mechanism of cell death induced by the most effective MTX salts.
Main Methods:
- Synthesis and characterization of twelve MTX salts using NMR spectroscopy and elemental analysis.
- In vitro antiproliferative assays using A549 and H1975 lung cancer cell lines.
- Apoptosis, necrosis, and reactive oxygen species (ROS) assays to determine the mechanism of action.
Main Results:
- Three MTX salts exhibited significant antiproliferative effects in A549 cells, with IC50 values as low as 0.55 ± 0.25 for [C12mim]2[MTX].
- The most effective salts demonstrated superior activity compared to other tested formulations.
- These salts induced intrinsic apoptosis and avoided necrosis and ROS formation, suggesting a targeted cell death mechanism.
Conclusions:
- Novel MTX salts can be designed to enhance antiproliferative activity against lung cancer.
- Specific MTX salts show promising efficacy and a favorable mechanism of action, inducing apoptosis without significant toxicity.
- These findings support further investigation of these MTX salts as potential lung cancer therapeutics.
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