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The correlation between telomerase activity and Bax/Bcl-2 ratio in valproic acid-treated MCF-7 breast cancer cell line.

Vafaiyan Z, Gharaei R, Asadi J - Iran J Basic Med Sci (2015)

Bottom Line: The results also showed that there is a significant correlation between reduction of telomerase activity and increase in Bax/Bcl-2 ratio (P=0.001).Our study demonstrated that cell viability of MCF-7 cells was decreased after treatment with VPA, probably through a reduction of telomerase activity and an increase in Bax/bcl-2 ratio.Therefore, it could be concluded that VPA is a potent anti-cancer agent for breast cancer cells through inhibition of telomerase activity and induction of apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, Disorder Metabolic Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

ABSTRACT

Objectives: Valproic acid (VPA), a drug used in the treatment of neurological disorders, has been shown to have cytotoxic effects on cancer cells through different mechanisms. Telomerase, a ribonucleoprotein reverse transcriptase, is responsible for elongation of the telomere and is activated in cancers. A relation between telomerase activity and resistance to apoptosis has been established. This study focused on probable effects of VPA on MCF-7 cancer cells. In particular, we investigated VPA effects on viability, apoptosis and telomerase activity.

Materials and methods: Cytotoxicity effects of VPA on MCF-7 cells were determined by neutral red uptake assay. Cells were treated with different concentrations of VPA (0-32 mM) and telomerase activity and Bax and Bcl-2 protein levels were determined using TRAP assay (PCR-ELISA) method and ELISA method, respectively.

Results: The cytotoxic effects of different concentration of VPA on MCF-7 cells were observed as a reduction in cell viability and telomerase activity and altered expression of Bcl-2 family protein levels. The results also showed that there is a significant correlation between reduction of telomerase activity and increase in Bax/Bcl-2 ratio (P=0.001).

Conclusion: Our study demonstrated that cell viability of MCF-7 cells was decreased after treatment with VPA, probably through a reduction of telomerase activity and an increase in Bax/bcl-2 ratio. Therefore, it could be concluded that VPA is a potent anti-cancer agent for breast cancer cells through inhibition of telomerase activity and induction of apoptosis.

No MeSH data available.


Related in: MedlinePlus

The effect of different concentrations of Valproic acid (VPA) (means ± SD) treatment for 24, 48 and72 hr on Bcl-2 expression. The amount of Bcl-2 protein significantly decreased after 48 hr (*P<0.05 and **P<0.005) and 72 hr (#P<0.05 and ##P<0.005) compared to 24 hr. The amount of Bcl-2 protein is also decreased after 72 hr (ᴥP<0.05 and ᴥᴥP<0.005) compared to 48 hr
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Figure 4: The effect of different concentrations of Valproic acid (VPA) (means ± SD) treatment for 24, 48 and72 hr on Bcl-2 expression. The amount of Bcl-2 protein significantly decreased after 48 hr (*P<0.05 and **P<0.005) and 72 hr (#P<0.05 and ##P<0.005) compared to 24 hr. The amount of Bcl-2 protein is also decreased after 72 hr (ᴥP<0.05 and ᴥᴥP<0.005) compared to 48 hr

Mentions: Bax, Bcl-2 and Bax / Bcl-2 were measured following 24, 48 and 72 hr treatment with different concentra- tions of VPA (0, 2, 8, 16 mM). Bax protein levels were augmented by increasing concentrations of VPA, and maximum protein concentration was obtained at 16 mM after 48 hr of treatment (Figure 3). Bcl-2 protein levels decreased with increasing concentrations of VPA and the lowest value was obtained at 16 mM following 72 hr treatment (Figure 4). Bax / Bcl-2 Ratio was also increased with increasing concentrations of valproic acid and showed the highest value at 16 mM in 48 hr (Figure 5).


The correlation between telomerase activity and Bax/Bcl-2 ratio in valproic acid-treated MCF-7 breast cancer cell line.

Vafaiyan Z, Gharaei R, Asadi J - Iran J Basic Med Sci (2015)

The effect of different concentrations of Valproic acid (VPA) (means ± SD) treatment for 24, 48 and72 hr on Bcl-2 expression. The amount of Bcl-2 protein significantly decreased after 48 hr (*P<0.05 and **P<0.005) and 72 hr (#P<0.05 and ##P<0.005) compared to 24 hr. The amount of Bcl-2 protein is also decreased after 72 hr (ᴥP<0.05 and ᴥᴥP<0.005) compared to 48 hr
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556764&req=5

Figure 4: The effect of different concentrations of Valproic acid (VPA) (means ± SD) treatment for 24, 48 and72 hr on Bcl-2 expression. The amount of Bcl-2 protein significantly decreased after 48 hr (*P<0.05 and **P<0.005) and 72 hr (#P<0.05 and ##P<0.005) compared to 24 hr. The amount of Bcl-2 protein is also decreased after 72 hr (ᴥP<0.05 and ᴥᴥP<0.005) compared to 48 hr
Mentions: Bax, Bcl-2 and Bax / Bcl-2 were measured following 24, 48 and 72 hr treatment with different concentra- tions of VPA (0, 2, 8, 16 mM). Bax protein levels were augmented by increasing concentrations of VPA, and maximum protein concentration was obtained at 16 mM after 48 hr of treatment (Figure 3). Bcl-2 protein levels decreased with increasing concentrations of VPA and the lowest value was obtained at 16 mM following 72 hr treatment (Figure 4). Bax / Bcl-2 Ratio was also increased with increasing concentrations of valproic acid and showed the highest value at 16 mM in 48 hr (Figure 5).

Bottom Line: The results also showed that there is a significant correlation between reduction of telomerase activity and increase in Bax/Bcl-2 ratio (P=0.001).Our study demonstrated that cell viability of MCF-7 cells was decreased after treatment with VPA, probably through a reduction of telomerase activity and an increase in Bax/bcl-2 ratio.Therefore, it could be concluded that VPA is a potent anti-cancer agent for breast cancer cells through inhibition of telomerase activity and induction of apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, Disorder Metabolic Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

ABSTRACT

Objectives: Valproic acid (VPA), a drug used in the treatment of neurological disorders, has been shown to have cytotoxic effects on cancer cells through different mechanisms. Telomerase, a ribonucleoprotein reverse transcriptase, is responsible for elongation of the telomere and is activated in cancers. A relation between telomerase activity and resistance to apoptosis has been established. This study focused on probable effects of VPA on MCF-7 cancer cells. In particular, we investigated VPA effects on viability, apoptosis and telomerase activity.

Materials and methods: Cytotoxicity effects of VPA on MCF-7 cells were determined by neutral red uptake assay. Cells were treated with different concentrations of VPA (0-32 mM) and telomerase activity and Bax and Bcl-2 protein levels were determined using TRAP assay (PCR-ELISA) method and ELISA method, respectively.

Results: The cytotoxic effects of different concentration of VPA on MCF-7 cells were observed as a reduction in cell viability and telomerase activity and altered expression of Bcl-2 family protein levels. The results also showed that there is a significant correlation between reduction of telomerase activity and increase in Bax/Bcl-2 ratio (P=0.001).

Conclusion: Our study demonstrated that cell viability of MCF-7 cells was decreased after treatment with VPA, probably through a reduction of telomerase activity and an increase in Bax/bcl-2 ratio. Therefore, it could be concluded that VPA is a potent anti-cancer agent for breast cancer cells through inhibition of telomerase activity and induction of apoptosis.

No MeSH data available.


Related in: MedlinePlus