ArticleMolecular cancer therapeutics2014
Targeting multiple key signaling pathways in melanoma using leelamine.
Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 50 citations in OpenAlex.
- TNFα activation of the PLEKHA5-FCRLA axis disturbs lipid metabolism, leading to the progression of cutaneous malignant melanoma.Lipids in health and disease · 2025Article
- Variations in the fetal bovine serum and glucose concentration in the culture medium impact the viability of glioblastoma cells as evidenced through the modulation of cell cycle and reactive oxygen species: AnJournal of biological methods · 2025Article
- Vitamin D3 reduces the viability of cancer cells in vitro and retard the EAC tumors growth in mice.PloS one · 2025Article
- Dehydroabietylamine exerts antitumor effects by affecting nucleotide metabolism in gastric cancer.Carcinogenesis · 2024Article
- Metal free cross-dehydrogenative N-N coupling of primary amides with Lewis basic amines.Nature communications · 2024Article
- In Vitro Cytotoxic Effects of Ferruginol Analogues in Sk-MEL28 Human Melanoma Cells.International journal of molecular sciences · 2023Article
- Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1.International journal of molecular sciences · 2023Review
- Leelamine Modulates STAT5 Pathway Causing Both Autophagy and Apoptosis in Chronic Myelogenous Leukemia Cells.Biology · 2022Article
- Targeted Inhibition of Anti-Inflammatory Regulator Nrf2 Results in Breast Cancer Retardation In Vitro and In Vivo.Biomedicines · 2021Article
- Natural Phytochemicals Derived from Gymnosperms in the Prevention and Treatment of Cancers.International journal of molecular sciences · 2021Review
- Design, Synthesis, and Molecular Docking Study of New Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Inhibitors Combining Resin Acids and Adamantane Moieties.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Leelamine suppresses cMyc expression in prostate cancer cellsJournal of cancer metastasis and treatment · 2021Article
- Lipid metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives.Cancers · 2020Review
- A Brief Overview of the Antitumoral Actions of Leelamine.Biomedicines · 2019Review
- Advances in Rosin-Based Chemicals: The Latest Recipes, Applications and Future Trends.Molecules (Basel, Switzerland) · 2019Review
- Synthesis and potential antineoplastic activity of dehydroabietylamine imidazole derivatives.MedChemComm · 2018Article
- Therapeutic Potential of Leelamine, a Novel Inhibitor of Androgen Receptor and Castration-Resistant Prostate Cancer.Molecular cancer therapeutics · 2018Article
- Nanoliposomal delivery of cytosolic phospholipase ANanomedicine : nanotechnology, biology, and medicine · 2018Article
- Identification of WEE1 as a target to make AKT inhibition more effective in melanoma.Cancer biology & therapy · 2018Article
- Improving pharmacological targeting of AKT in melanoma.Cancer letters · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Melanoma is a highly drug-resistant cancer with resistance developing to agents targeting single proteins. To circumvent this problem, a new class of agent inhibiting multiple key pathways important in this disease is being developed to reduce the likelihood of developing resistant disease. The phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), and STAT3 pathways are constitutively activated in 50% to 70% of melanomas, promoting disease development. To identify a drug simultaneously targeting the PI3K, MAPK, and STAT3 cascades, a natural product library was screened to identify leelamine as a potential inhibitor. Leelamine was 4.5-fold more effective at inhibiting cultured melanoma cell survival than normal cells, with average IC(50) values of 2 and 9.3 μmol/L, respectively. It inhibited cellular proliferation at a concentration of 2.5 μmol/L by 40% to 80% and longer exposure increased apoptosis 600%. Leelamine inhibited the growth of preexisting xenografted melanoma tumors by an average of 60% by targeting the PI3K, MAPK, and STAT3 pathways without affecting animal body weight or blood markers of major organ function. The mechanism of action of leelamine is mediated by disruption of cholesterol transport, causing decreased cellular proliferation and consequently leading to increased tumor cell apoptosis as well as decreased tumor vascularization. Thus, a unique agent and novel mechanism of action has been identified for the treatment of melanoma that acts by inhibiting the activity of three major signaling pathways regulating the development of this disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.