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Phenethyl isothiocyanate suppresses cervical carcinoma metastasis potential and its molecular mechanism
Li Zhang1, Quan Hao1, Lewen Bao1
1Department of Gynecologic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
Abstract:
Tumor metastasis is a prominent cause of treatment failure in cervical carcinoma. Phenethyl isothiocyanate (PEITC) is an active component extracted from cruciferous plants that has exhibited anticancer activity in various types of human cancer; however, its effect on the inhibition of metastasis remains unclear. The current study aimed to explore the effect of PEITC on the suppression of metastasis in HeLa cervical carcinoma cells. Multiple variables were assessed with different methods as follows: Cell viability, with a Vi‑CELL analyzer; cell adhesion, by MTS assay; cell invasion, by Transwell assay; cell cycle, by flow cytometry assay; cytokine concentration, by ELISA assay; metastasis‑related gene and protein expression, by quantitative polymerase chain reaction and western blotting; and transcription factor activity, by gene reporter assay. The results indicated that PEITC exhibited an inhibitory effect on the adhesion and invasion of HeLa cells by induction of G2/M phase arrest, it reduced the expression of CDK1, MMP‑2/9, CD44, ICAM‑1, increased the production of TGF‑β, IL‑6 and IL‑8, and increased the phosphorylation of Smad2. These results suggest that PEITC may be a potential antitumor compound, acting through the TGF‑β/Smad2 pathway; and it has the potential for future use as a therapy for cervical carcinoma subsequent to further studies.
Insights
Phenethyl isothiocyanate (PEITC) inhibits cervical cancer metastasis by blocking cell adhesion and invasion. This compound may offer a new therapeutic strategy for cervical carcinoma by targeting the TGF-β/Smad2 pathway.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tumor metastasis is a primary reason for treatment failure in cervical carcinoma.
- Phenethyl isothiocyanate (PEITC), derived from cruciferous plants, shows anticancer properties, but its anti-metastatic effects are not well-understood.
Purpose of the Study:
- To investigate the potential of PEITC in suppressing metastasis in HeLa cervical carcinoma cells.
- To elucidate the molecular mechanisms underlying PEITC's anti-metastatic activity.
Main Methods:
- Assessed cell viability (Vi-CELL), adhesion (MTS assay), invasion (Transwell assay), and cell cycle progression (flow cytometry).
- Quantified cytokine production (ELISA), gene and protein expression (qPCR, Western blotting), and transcription factor activity (gene reporter assay).
Main Results:
- PEITC inhibited HeLa cell adhesion and invasion, inducing G2/M phase arrest.
- PEITC reduced expression of CDK1, MMP-2/9, CD44, and ICAM-1.
- PEITC increased TGF-β, IL-6, IL-8 production and Smad2 phosphorylation, suggesting activation of the TGF-β/Smad2 pathway.
Conclusions:
- PEITC demonstrates significant anti-metastatic potential in cervical carcinoma cells.
- The anti-metastatic effects are mediated through the TGF-β/Smad2 signaling pathway.
- PEITC warrants further investigation as a potential therapeutic agent for cervical cancer.
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