Related Experiment Video
Updated: Sep 9, 2025
Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Imipramine Inhibits Osteosarcoma Invasion via Src Inactivation and Caspase-Dependent Apoptosis
Yu-Chang Liu1,2, Chi-Jung Fang3, Li-Cho Hsu4
1Department of Radiation Oncology, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan, ROC.
Abstract:
Osteosarcoma (OS) is an aggressive malignancy characterised by high metastatic potential and poor prognosis. Imipramine, a tricyclic antidepressant, has shown potential anticancer effects. This study evaluates the cytotoxic, pro-apoptotic and anti-invasion effects of imipramine on OS cells in vitro and in vivo, as well as its underlying mechanisms. Imipramine significantly reduced U-2 OS and MG 63 cell viability in a time- and dose-dependent manner, confirmed through MTT and colony formation assays. It induced apoptosis via caspase-dependent pathways, as evidenced by increased cleaved caspase-3, -8 and -9 levels and reduced expression of anti-apoptotic proteins such as MCL-1. Imipramine activated both extrinsic and intrinsic apoptosis pathways in vitro and in vivo, increasing Fas, Fas-L, BAX and BAK while suppressing anti-apoptotic factors like BCL-2 and XIAP. Transwell assays showed dose-dependent inhibition of cell migration and invasion, supported by suppressed Src phosphorylation and downregulation of EMT markers (Snail-1 and Slug). In U-2 OS xenograft-bearing mice, imipramine significantly inhibited tumour growth in a dose-dependent manner, with the 30 mg/kg group showing the smallest tumour volume and slowest growth rate (p = 0.0098). Tumour weights were significantly reduced without impacting body weight or liver and kidney function markers (AST, ALT, γ-GT and CREA). Histopathological analyses revealed no significant abnormalities in vital organs. Imipramine exerts potent anti-OS effects by suppressing Src-mediated invasion and enhancing caspase-dependent apoptosis through extrinsic and intrinsic pathways. It inhibits tumour progression without inducing systemic toxicity, demonstrating its potential as a therapeutic candidate for OS.
Insights
Imipramine, an antidepressant, effectively combats osteosarcoma (OS) by inducing cancer cell death and inhibiting invasion. This study shows imipramine reduces tumor growth in vivo without causing significant toxicity, highlighting its therapeutic potential for OS.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Osteosarcoma (OS) is an aggressive bone cancer with high metastatic potential and poor patient outcomes.
- Imipramine, a tricyclic antidepressant, has demonstrated potential anticancer properties warranting further investigation.
- Understanding the mechanisms of imipramine's anti-OS effects is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To evaluate the cytotoxic, pro-apoptotic, and anti-invasion effects of imipramine on osteosarcoma cells.
- To elucidate the underlying molecular mechanisms of imipramine's action against OS.
- To assess the efficacy and safety of imipramine in preclinical osteosarcoma models.
Main Methods:
- In vitro studies utilized MTT and colony formation assays to assess cell viability and imipramine's cytotoxic effects.
- Apoptosis was analyzed by measuring caspase activation and the expression of apoptosis-related proteins (e.g., BAX, BCL-2, MCL-1, XIAP).
- In vivo efficacy was evaluated using U-2 OS xenograft mouse models, assessing tumor growth, weight, and systemic toxicity through biochemical and histopathological analyses.
Main Results:
- Imipramine significantly reduced osteosarcoma cell viability and proliferation in a dose- and time-dependent manner.
- The drug induced apoptosis through both caspase-dependent extrinsic and intrinsic pathways, modulating key apoptotic proteins.
- Imipramine suppressed cell migration and invasion by inhibiting Src phosphorylation and downregulating epithelial-mesenchymal transition (EMT) markers.
- In vivo, imipramine significantly inhibited tumor growth in xenograft models without causing adverse effects on body weight or vital organ function.
Conclusions:
- Imipramine demonstrates potent anti-osteosarcoma activity by enhancing apoptosis and inhibiting invasion via Src signaling.
- The drug effectively reduces tumor progression in vivo with a favorable safety profile.
- Imipramine holds promise as a potential therapeutic agent for osteosarcoma treatment.
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
02:34Inhibition of Cdk Activity
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:20The JAK-STAT Signaling Pathway