Imipramine Induces Apoptosis and Inhibits the Metastatic Potential of Triple-negative Breast Cancer Cells
Sheng-Kai Chen1, Wei Lee2,3, Yu-Ching Li4
1Department of Nuclear Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
Background/Aim:
Triple-negative breast cancer (TNBC) is an aggressive and deadly subtype of breast cancer, and there is an urgent need for new therapeutic strategies. The highly metastatic and anti-apoptotic characteristics are known to be the major factors causing uncontrolled growth in TNBC. Imipramine is a tricyclic antidepressant that possesses anti-inflammatory activity and has been reported to inhibit the progression of highly metastatic non-small cell lung cancer.
Materials And Methods:
This study used MTT assay, apoptosis markers flow cytometry analysis, open-source data analysis, NF-B reporter gene assay, and western blotting to elucidate the effect of imipramine on MDA-MB-231 and 4T1 cells.
Results:
Imipramine induced caspase-mediated extrinsic and intrinsic apoptosis and was potentially associated with patient overall survival. Furthermore, imipramine suppressed the invasion and migration abilities and the expression of metastasis-associated proteins in TNBC cells.
Conclusion:
Imipramine effectively suppressed TNBC progression by inducing apoptosis and inhibiting metastasis.
Insights
Imipramine effectively combats triple-negative breast cancer (TNBC) by inducing cell death and reducing metastasis. This antidepressant shows promise in suppressing aggressive tumor growth and improving patient outcomes.
Area of Science:
- Oncology
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive cancer subtype with limited therapeutic options.
- Metastasis and resistance to apoptosis drive TNBC progression.
- Imipramine, an antidepressant, exhibits anti-inflammatory properties and has shown efficacy against lung cancer metastasis.
Purpose of the Study:
- To investigate the therapeutic potential of imipramine in triple-negative breast cancer.
- To elucidate the mechanisms by which imipramine affects TNBC cell growth, apoptosis, and metastasis.
Main Methods:
- MTT assay for cell viability.
- Flow cytometry for apoptosis analysis.
- NF-κB reporter gene assay and Western blotting for molecular mechanisms.
- Analysis of open-source patient data.
Main Results:
- Imipramine induced caspase-mediated apoptosis through both extrinsic and intrinsic pathways.
- Imipramine suppressed the invasion and migration of TNBC cells.
- Imipramine reduced the expression of metastasis-associated proteins.
- Imipramine's effects were potentially linked to improved patient overall survival.
Conclusions:
- Imipramine demonstrates significant potential as a therapeutic agent for TNBC.
- Imipramine effectively suppresses TNBC progression by inducing apoptosis and inhibiting metastasis.
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