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Mini profile of potential anticancer properties of propofol.

Song J, Shen Y, Zhang J, Lian Q - PLoS ONE (2014)

Bottom Line: We demonstrated that the expression level of caspase-3, an apoptosis biomarker, significantly increased in a dose-dependent manner after 24-h stimulation with 100 µM propofol in A549 cells, and slightly increased in LoVo cells.High caspase-3 expression in A549 cells may be modulated by the ERK1/2 pathway because phosphorylated ERK1/2 dramatically reduced after propofol treatment.Our results suggest that the anti-cancer effects of propofol, which are consistent with those of previous studies, are likely associated with the Kras mutation status.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Montefiore Medical Center, New York, New York, United States of America.

ABSTRACT

Background: Propofol (2, 6-diisopropylphenol) is an intravenous sedative-hypnotic agent administered to induce and maintain anesthesia. It has been recently revealed that propofol has anticancer properties including direct and indirect suppression of the viability and proliferation of cancer cells by promoting apoptosis in some cancer cell lines.

Methodology/principal findings: This study aimed to establish a profile to quantitatively and functionally evaluate the anticancer properties of propofol in three cancer cell lines: non-small cell lung carcinoma cell line A549, human colon carcinoma cell line LoVo, and human breast cancer cell line SK-BR-3. We demonstrated that the expression level of caspase-3, an apoptosis biomarker, significantly increased in a dose-dependent manner after 24-h stimulation with 100 µM propofol in A549 cells, and slightly increased in LoVo cells. However, there was no change in caspase-3 expression in SK-BR-3 cells. High caspase-3 expression in A549 cells may be modulated by the ERK1/2 pathway because phosphorylated ERK1/2 dramatically reduced after propofol treatment. BAX, a major protein that promotes apoptosis in the regulation phase, was highly expressed in A549 cells after treatment with 25 µM propofol. Apoptosis induced by propofol may be associated with cancer cells carrying Kras mutations.

Conclusions/significance: Our results suggest that the anti-cancer effects of propofol, which are consistent with those of previous studies, are likely associated with the Kras mutation status. Only Kras mutation in Codon 12 instead of other Kras status has been demonstrated to play an important role in sensitizing the propofol-induced apoptosis in cancer cell lines from our study. These findings may enable us a detailed investigation of propofol/Kras-mediated cancer cell apoptosis in the future.

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High Content Analysis of BAX expression in three cell lines.Propofol treatment increased the BAX expression in A549 cells treated for 6 hours with 25 µM of propofol. No change in BAX expression in all other groups and other two cell lines. (A) High content analysis of expression BAX in A549 cell treated with 25 µM of propofol for 6 hour. Nuclei were stained blue. BAX positive cells were stained green. Images were acquired at 5× magnification lens. (a) A549 cell treated with 0.5% DMSO for 6 hours. (b) A549 treated with 25 µM of propofol made with 0.5% DMSO for 6 hours. These results are representative of three independent experiments. (B) Charts indicate BAX expression in A549 (a), LoVo (b), and SKBR3 (c) lines with the induction of propofol for 6 hours. There is no BAX signal change after 24 hour treatment with all three concentrations of propofol for any of the three lines tested here. Each value was determined with Target Activation BioApplication Guide suggested by manufacturer (Thermo Scientific), and normalized to the expression of BAX with 0.5% DMSO incubation, and represents a mean of triplicate determinants. The results were evaluated by ANOVA test. A star () indicates statistically significant difference with the P<0.05.
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pone-0114440-g002: High Content Analysis of BAX expression in three cell lines.Propofol treatment increased the BAX expression in A549 cells treated for 6 hours with 25 µM of propofol. No change in BAX expression in all other groups and other two cell lines. (A) High content analysis of expression BAX in A549 cell treated with 25 µM of propofol for 6 hour. Nuclei were stained blue. BAX positive cells were stained green. Images were acquired at 5× magnification lens. (a) A549 cell treated with 0.5% DMSO for 6 hours. (b) A549 treated with 25 µM of propofol made with 0.5% DMSO for 6 hours. These results are representative of three independent experiments. (B) Charts indicate BAX expression in A549 (a), LoVo (b), and SKBR3 (c) lines with the induction of propofol for 6 hours. There is no BAX signal change after 24 hour treatment with all three concentrations of propofol for any of the three lines tested here. Each value was determined with Target Activation BioApplication Guide suggested by manufacturer (Thermo Scientific), and normalized to the expression of BAX with 0.5% DMSO incubation, and represents a mean of triplicate determinants. The results were evaluated by ANOVA test. A star () indicates statistically significant difference with the P<0.05.

Mentions: To determine the effects of propofol on the induction of apoptosis for these three cell lines (A549, LoVo, and SKBR3), BAX was selected. BAX expression level was significantly high after a 6 hour treatment with 25 µM propofol in A549 cells (Fig. 2). There were, however, no changes in the 50 µM or 100 µM groups at either the 6 hour or 24 hour time points. Additionally, there was no change in BAX expression in either LoVo or SKBR3 cells treated with 25 µM, 50 µM or 100 µM of propofol.


Mini profile of potential anticancer properties of propofol.

Song J, Shen Y, Zhang J, Lian Q - PLoS ONE (2014)

High Content Analysis of BAX expression in three cell lines.Propofol treatment increased the BAX expression in A549 cells treated for 6 hours with 25 µM of propofol. No change in BAX expression in all other groups and other two cell lines. (A) High content analysis of expression BAX in A549 cell treated with 25 µM of propofol for 6 hour. Nuclei were stained blue. BAX positive cells were stained green. Images were acquired at 5× magnification lens. (a) A549 cell treated with 0.5% DMSO for 6 hours. (b) A549 treated with 25 µM of propofol made with 0.5% DMSO for 6 hours. These results are representative of three independent experiments. (B) Charts indicate BAX expression in A549 (a), LoVo (b), and SKBR3 (c) lines with the induction of propofol for 6 hours. There is no BAX signal change after 24 hour treatment with all three concentrations of propofol for any of the three lines tested here. Each value was determined with Target Activation BioApplication Guide suggested by manufacturer (Thermo Scientific), and normalized to the expression of BAX with 0.5% DMSO incubation, and represents a mean of triplicate determinants. The results were evaluated by ANOVA test. A star () indicates statistically significant difference with the P<0.05.
© Copyright Policy
Related In: Results  -  Collection

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pone-0114440-g002: High Content Analysis of BAX expression in three cell lines.Propofol treatment increased the BAX expression in A549 cells treated for 6 hours with 25 µM of propofol. No change in BAX expression in all other groups and other two cell lines. (A) High content analysis of expression BAX in A549 cell treated with 25 µM of propofol for 6 hour. Nuclei were stained blue. BAX positive cells were stained green. Images were acquired at 5× magnification lens. (a) A549 cell treated with 0.5% DMSO for 6 hours. (b) A549 treated with 25 µM of propofol made with 0.5% DMSO for 6 hours. These results are representative of three independent experiments. (B) Charts indicate BAX expression in A549 (a), LoVo (b), and SKBR3 (c) lines with the induction of propofol for 6 hours. There is no BAX signal change after 24 hour treatment with all three concentrations of propofol for any of the three lines tested here. Each value was determined with Target Activation BioApplication Guide suggested by manufacturer (Thermo Scientific), and normalized to the expression of BAX with 0.5% DMSO incubation, and represents a mean of triplicate determinants. The results were evaluated by ANOVA test. A star () indicates statistically significant difference with the P<0.05.
Mentions: To determine the effects of propofol on the induction of apoptosis for these three cell lines (A549, LoVo, and SKBR3), BAX was selected. BAX expression level was significantly high after a 6 hour treatment with 25 µM propofol in A549 cells (Fig. 2). There were, however, no changes in the 50 µM or 100 µM groups at either the 6 hour or 24 hour time points. Additionally, there was no change in BAX expression in either LoVo or SKBR3 cells treated with 25 µM, 50 µM or 100 µM of propofol.

Bottom Line: We demonstrated that the expression level of caspase-3, an apoptosis biomarker, significantly increased in a dose-dependent manner after 24-h stimulation with 100 µM propofol in A549 cells, and slightly increased in LoVo cells.High caspase-3 expression in A549 cells may be modulated by the ERK1/2 pathway because phosphorylated ERK1/2 dramatically reduced after propofol treatment.Our results suggest that the anti-cancer effects of propofol, which are consistent with those of previous studies, are likely associated with the Kras mutation status.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Montefiore Medical Center, New York, New York, United States of America.

ABSTRACT

Background: Propofol (2, 6-diisopropylphenol) is an intravenous sedative-hypnotic agent administered to induce and maintain anesthesia. It has been recently revealed that propofol has anticancer properties including direct and indirect suppression of the viability and proliferation of cancer cells by promoting apoptosis in some cancer cell lines.

Methodology/principal findings: This study aimed to establish a profile to quantitatively and functionally evaluate the anticancer properties of propofol in three cancer cell lines: non-small cell lung carcinoma cell line A549, human colon carcinoma cell line LoVo, and human breast cancer cell line SK-BR-3. We demonstrated that the expression level of caspase-3, an apoptosis biomarker, significantly increased in a dose-dependent manner after 24-h stimulation with 100 µM propofol in A549 cells, and slightly increased in LoVo cells. However, there was no change in caspase-3 expression in SK-BR-3 cells. High caspase-3 expression in A549 cells may be modulated by the ERK1/2 pathway because phosphorylated ERK1/2 dramatically reduced after propofol treatment. BAX, a major protein that promotes apoptosis in the regulation phase, was highly expressed in A549 cells after treatment with 25 µM propofol. Apoptosis induced by propofol may be associated with cancer cells carrying Kras mutations.

Conclusions/significance: Our results suggest that the anti-cancer effects of propofol, which are consistent with those of previous studies, are likely associated with the Kras mutation status. Only Kras mutation in Codon 12 instead of other Kras status has been demonstrated to play an important role in sensitizing the propofol-induced apoptosis in cancer cell lines from our study. These findings may enable us a detailed investigation of propofol/Kras-mediated cancer cell apoptosis in the future.

Show MeSH
Related in: MedlinePlus