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Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
Published on: April 2, 2020
Bisdemethoxycurcumin suppresses human osteosarcoma U‑2 OS cell migration and invasion via affecting the
Yi-Shih Ma1, Shu-Fen Peng2, Rick Sai-Chuen Wu3
1School of Chinese Medicine for Post‑Baccalaureate, College of Medicine, I‑Shou University, Kaohsiung 82445, Taiwan, R.O.C.
Abstract:
The metastasis of human osteosarcoma (OS) shows a difficult‑to‑treat clinical scenario and results in decreased quality of life and diminished survival rates. Finding or developing novel treatments to improve the life quality of patients is urgent. Bisdemethoxycurcumin (BDMC), a natural product, was obtained from the rhizome of turmeric (Curcuma longa) and exerts antitumor activities in numerous human cancer cell lines. At present, there is no study showing BDMC effects on OS cell migration and invasion. In the present study, the effects of BDMC on cell migration and invasion of OS U‑2 OS cells were investigated in vitro. Cell viability and proliferation were measured by flow cytometric and MTT assays, respectively. Cell motility, MMP‑2 and ‑9 activity, and cell migration and invasion were assayed by scratch wound healing, gelatin zymography, and Transwell chamber assays, respectively. The protein expression levels were measured by western blotting. BDMC at 20 and 40 µM significantly reduced total cell viability, and BDMC at 5 and 10 µM significantly inhibited cell motility in U‑2 OS cells. BDMC significantly suppressed the activities of MMP‑2 and MMP‑9 in U‑2 OS cells. BDMC suppressed cell invasion and migration after 24 h treatment in U‑2 OS cells, and these effects were in a dose‑dependently manner. Results from western blotting indicated that BDMC significantly decreased the protein expression levels of PI3K/Akt/NF‑κB, PI3K/Akt/GSK3β, and MAPK pathway in U‑2 OS cells. Furthermore, BDMC inhibited uPA, MMP‑2, MMP‑9, MMP‑13, N‑cadherin, VE‑cadherin, and vimentin but increased E‑cadherin in U‑2 OS cells. Based on these observations, it was suggested that BDMC may be a potential candidate against migration and invasion of human OS cells in the future.
Insights
Bisdemethoxycurcumin (BDMC) from turmeric shows potential in treating osteosarcoma (OS) metastasis. This natural compound effectively inhibited OS cell migration and invasion in vitro, suggesting a novel therapeutic avenue.
Area of Science:
- Biochemistry and Molecular Biology
- Cancer Research
- Natural Product Chemistry
Background:
- Metastatic human osteosarcoma (OS) presents a significant clinical challenge, leading to reduced survival and quality of life.
- Novel therapeutic strategies are urgently needed to combat OS metastasis.
- Bisdemethoxycurcumin (BDMC), a natural compound from turmeric (Curcuma longa), exhibits known antitumor properties but its effects on OS cell migration and invasion were unstudied.
Purpose of the Study:
- To investigate the in vitro effects of Bisdemethoxycurcumin (BDMC) on the migration and invasion of human osteosarcoma (OS) U-2 OS cells.
- To explore the molecular mechanisms underlying BDMC's potential anti-metastatic activity in OS.
Main Methods:
- Cell viability and proliferation assessed using flow cytometry and MTT assays.
- Cell motility, migration, and invasion evaluated via scratch wound healing and Transwell chamber assays.
- Matrix metalloproteinase (MMP) activity determined by gelatin zymography.
- Protein expression levels of key signaling pathways (PI3K/Akt/NF-κB, PI3K/Akt/GSK3β, MAPK) and metastasis-associated proteins analyzed by western blotting.
Main Results:
- BDMC significantly reduced osteosarcoma cell viability and motility in a dose-dependent manner.
- BDMC suppressed the enzymatic activities of MMP-2 and MMP-9, crucial for extracellular matrix degradation.
- BDMC treatment inhibited cell migration and invasion, decreased protein expression of PI3K/Akt/NF-κB, PI3K/Akt/GSK3β, and MAPK pathways, and modulated metastasis-related proteins (inhibited uPA, MMP-2, MMP-9, MMP-13, N-cadherin, VE-cadherin, vimentin; increased E-cadherin).
Conclusions:
- Bisdemethoxycurcumin (BDMC) demonstrates significant anti-migratory and anti-invasive effects on human osteosarcoma (OS) U-2 OS cells in vitro.
- BDMC exerts its effects by downregulating key signaling pathways (PI3K/Akt/NF-κB, PI3K/Akt/GSK3β, MAPK) and altering the expression of metastasis-associated proteins.
- BDMC is a promising candidate for developing novel therapeutic strategies against osteosarcoma metastasis.
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