Anticancer activity of fluoxetine Janus dendrimer against cancer cells
Marcos Martínez-García1, Isabel Hernández-Rioja1, Israel Barajas-Mendoza1
1Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, México.
Abstract:
Targeting the inflammation-related molecules with nonsteroidal anti-inflammatory drugs (NSAIDs) represents a promising approach for cancer prevention/therapy. We evaluated the in vitro anticancer effects of sulindac, ketoprofen, celecoxib and the antidepressant fluoxetine, both free and coupled with synthesized dendrons and dendrimers, on the proliferation and apoptosis of human MCF-7 (human mammary adenocarcinoma), SKLU-1 (human lung adenocarcinoma) and as a control the normal monkey kidney (COS-7) cell line. The antiproliferative activity and cytotoxicity of tested NSAIDs on MCF-7 and SKLU-1 cell lines were assessed by the sulforhodamine B (SRB) assay. The tested dendrons with NSAIDs showed activity against the tumour cell lines. Significant inhibition of the growth of cancer cells was observed for the Janus dendrimers with sulindac-celecoxib, which was selective against MCF-7; and Janus dendrimers with fluoxetine were highly cytotoxic. The fluoxetine-dendrimer could be a candidate for the development of new pharmacological strategies for the treatment and prevention of MCF-7 cancer.
Insights
Nonsteroidal anti-inflammatory drugs (NSAIDs) coupled with dendrimers show promise for cancer therapy. Janus dendrimers with fluoxetine demonstrated high cytotoxicity, suggesting potential for novel MCF-7 cancer treatment strategies.
Area of Science:
- Pharmacology and Oncology
- Nanotechnology in Medicine
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) target inflammation-related molecules, offering potential for cancer prevention and therapy.
- Dendrimers and dendrons are synthetic macromolecules with potential applications in drug delivery and cancer treatment.
Purpose of the Study:
- To evaluate the in vitro anticancer effects of NSAIDs (sulindac, ketoprofen, celecoxib) and fluoxetine, both alone and conjugated with dendrons/dendrimers.
- To assess the impact on proliferation and apoptosis in human breast (MCF-7) and lung (SKLU-1) adenocarcinoma cell lines, using normal monkey kidney (COS-7) cells as a control.
Main Methods:
- In vitro evaluation of antiproliferative activity and cytotoxicity using the sulforhodamine B (SRB) assay.
- Testing of free drugs and drugs conjugated with synthesized dendrons and dendrimers on cancer cell lines.
Main Results:
- Dendrons with NSAIDs exhibited activity against the tested tumor cell lines.
- Janus dendrimers with a sulindac-celecoxib combination showed selective growth inhibition against MCF-7 cells.
- Janus dendrimers conjugated with fluoxetine displayed significant cytotoxicity.
Conclusions:
- The fluoxetine-dendrimer conjugate shows potential as a candidate for developing new pharmacological strategies for MCF-7 cancer treatment and prevention.
- Dendrimer conjugation can enhance the anticancer efficacy and selectivity of NSAIDs and other therapeutic agents.
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