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Published on: March 18, 2014
Anticancer Effects of Nortriptyline Hydrochloride in Osteosarcoma Cells Including Doxorubicin-resistant Cells
Yuki Uemichi1, Miyuki Mabuchi1, Shuji Nagano1
1School of Pharmacy, Hyogo Medical University, Kobe, Japan.
Background/Aim:
Osteosarcoma (OS), the most common primary malignant bone tumor, is associated with a high risk of recurrence and metastasis, leading to poor prognosis. This study explored the potential use of drug repositioning by investigating nortriptyline hydrochloride (NTP) in osteosarcoma treatment. NTP, a classic tricyclic antidepressant used to treat psychiatric disorders, has been shown to have antitumor activity against several cancer types.
Materials And Methods:
We investigated the inhibitory effects of NTP on OS cell proliferation and migration. The anticancer activity of NTP was evaluated in terms of cell viability, chemical rescue by cell death inhibitors, lactate dehydrogenase (LDH) release, cytoskeletal staining, and cell cycle analysis. NTP inhibited the proliferation of OS cells and induced G0/G1 phase cell cycle arrest in a dose-dependent manner.
Results:
The IC50 values of NTP were 24.2 μM and 15.8 μM for U2OS and MG-63 cell proliferation, respectively. Chemical rescue using cell death inhibitors and LDH release assays showed that the anticancer effects of NTP was mainly attributed to the inhibition of cell proliferation. Additionally, NTP inhibited cell migration, disrupted actin filament formation, and altered intracellular distribution. Furthermore, NTP retained growth inhibitory activity in doxorubicin-resistant OS cells.
Conclusion:
NTP may serve as a novel therapeutic agent for preventing OS growth and metastasis.
Insights
Nortriptyline hydrochloride (NTP) effectively inhibits osteosarcoma (OS) cell proliferation and migration. This drug repositioning approach shows promise for treating OS and preventing metastasis.
Area of Science:
- Oncology
- Pharmacology
- Drug Repositioning
Background:
- Osteosarcoma (OS) is a primary bone cancer with high recurrence and metastasis rates.
- Nortriptyline hydrochloride (NTP), an antidepressant, exhibits antitumor properties in various cancers.
Purpose of the Study:
- To investigate NTP's potential as a therapeutic agent for osteosarcoma.
- To explore drug repositioning of NTP for osteosarcoma treatment.
Main Methods:
- Assessed NTP's effects on OS cell proliferation and migration.
- Evaluated cell viability, cell death inhibition, LDH release, and cell cycle.
- Utilized cytoskeletal staining and doxorubicin-resistant OS cells.
Main Results:
- NTP inhibited OS cell proliferation and migration in a dose-dependent manner.
- NTP induced G0/G1 cell cycle arrest and disrupted actin filaments.
- NTP demonstrated efficacy against doxorubicin-resistant OS cells.
Conclusions:
- NTP exhibits significant anticancer activity against osteosarcoma cells.
- NTP shows potential as a novel therapeutic agent for osteosarcoma.
- NTP may prevent osteosarcoma growth and metastasis.
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