Related Experiment Video
Updated: Dec 21, 2025
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Anticancer Melatplatin Prodrugs: High Effect and Low Toxicity, MT1-ER-Target and Immune Response In Vivo
Xue-Qing Song1, Rui-Ping Liu1, Shu-Qing Wang1
1Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
Abstract:
Multitargeted therapy could rectify various oncogenic pathways to block tumorigenesis and progression. The combination of endocrine-, immune-, and chemotherapy might exert a highly synergistic effect against certain tumors. Herein, a series of smart Pt(IV) prodrugs 3-6, named Melatplatin, were rationally designed not only to multitarget DNA, MT1, and estrogen receptor (ER) but also to activate immune response. Melatplatin, conjugating first-line chemotherapeutic Pt drugs with human endogenous melatonin (MT), significantly enhanced drug efficacy especially in ER high-expression (ER+) cells, among which 3 presented the most potent cytotoxicity toward ER+ MCF-7 with nanomolar IC50 values 100-fold lower than cisplatin. Melatplatin could bind well to melatonin receptor (MT1) according to molecular docking. Besides, 3 evidently increased intracellular accumulation and DNA damage, upregulated γH2AX and P53, and silenced NF-κB to induce massive apoptosis. Most strikingly, 3 effectively inhibited tumor growth and attenuated systemic toxicity compared to cisplatin in vivo, promoting lymphocyte proliferation in spleen to achieve immune modulation.
Insights
This study introduces Melatplatin, a novel platinum(IV) prodrug that combines chemotherapy with melatonin to target cancer cells. Melatplatin shows enhanced efficacy against estrogen receptor-positive tumors and modulates the immune response, offering a promising multitargeted cancer therapy.
Area of Science:
- Oncology
- Pharmacology
- Immunology
Background:
- Multitargeted therapies offer a strategy to overcome tumor progression by simultaneously inhibiting multiple oncogenic pathways.
- Combining endocrine, immune, and chemotherapy may yield synergistic effects against various cancers.
- Platinum(IV) prodrugs conjugated with melatonin (Melatplatin) were designed for multitargeted cancer treatment.
Purpose of the Study:
- To design and synthesize novel platinum(IV) prodrugs (Melatplatin) for multitargeted therapy.
- To evaluate the efficacy of Melatplatin against estrogen receptor-positive (ER+) tumors and its mechanism of action.
- To assess the immunomodulatory effects and in vivo performance of Melatplatin compared to cisplatin.
Main Methods:
- Synthesis and characterization of platinum(IV) prodrugs (Melatplatin 3-6).
- In vitro cytotoxicity assays on ER+ MCF-7 cells and molecular docking with melatonin receptor 1 (MT1).
- Assessment of intracellular accumulation, DNA damage markers (γH2AX, P53), apoptosis induction (NF-κB silencing), and in vivo tumor growth inhibition and toxicity studies.
Main Results:
- Melatplatin demonstrated significantly enhanced efficacy in ER+ cells, with compound 3 showing 100-fold lower IC50 values than cisplatin.
- Molecular docking confirmed Melatplatin's binding affinity to MT1.
- Compound 3 increased intracellular drug accumulation, DNA damage, upregulated tumor suppressor proteins, silenced NF-κB, induced apoptosis, inhibited tumor growth in vivo, and promoted lymphocyte proliferation.
Conclusions:
- Melatplatin represents a smart multitargeted therapy approach, effectively inhibiting ER+ tumor growth via DNA damage and apoptosis induction.
- The drug exhibits potent cytotoxicity and favorable in vivo efficacy with reduced systemic toxicity compared to cisplatin.
- Melatplatin's ability to modulate immune response suggests its potential as an immunochemotherapy agent.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...