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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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Related in: MedlinePlus

Propofol treatment decreased ERK1/2 activation in A549 cells.(A) The Western Blot Image of time course of Phosphorylated ERK1/2 Expression in A549 Treated with 100 µM propofol. (B) The Quantification of the Western Blot. These results are representative of three independent experiments with a total of 15 samples. By using One Way ANOVA testing, we found the differences from all one-hour propofol groups to be significantly lower compared with the 0-hour group with a P value <0.0001. ANOVA was used to do the analysis.
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pone-0114440-g003: Propofol treatment decreased ERK1/2 activation in A549 cells.(A) The Western Blot Image of time course of Phosphorylated ERK1/2 Expression in A549 Treated with 100 µM propofol. (B) The Quantification of the Western Blot. These results are representative of three independent experiments with a total of 15 samples. By using One Way ANOVA testing, we found the differences from all one-hour propofol groups to be significantly lower compared with the 0-hour group with a P value <0.0001. ANOVA was used to do the analysis.

Mentions: ERK is one of the key factors in the Ras/Raf/MEK/ERK signaling pathway. This pathway promotes cell proliferation, cell survival and metastasis. Usually it is aberrantly activated in cancer [17]. The activation of ERK is associated with K-Ras mutation in cancer cells [18]). We next sought to determine the activation of ERK1/2 in K-Ras mutant A549 cells after propofol treatment. We found that the phosphorylated ERK1/2, the activated form of ERK1/2, started to decrease at 60 minutes after propofol treatment and returned to the basal level at 5 hour time point (Fig. 3).


Mini profile of potential anticancer properties of propofol.

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

Propofol treatment decreased ERK1/2 activation in A549 cells.(A) The Western Blot Image of time course of Phosphorylated ERK1/2 Expression in A549 Treated with 100 µM propofol. (B) The Quantification of the Western Blot. These results are representative of three independent experiments with a total of 15 samples. By using One Way ANOVA testing, we found the differences from all one-hour propofol groups to be significantly lower compared with the 0-hour group with a P value <0.0001. ANOVA was used to do the analysis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263663&req=5

pone-0114440-g003: Propofol treatment decreased ERK1/2 activation in A549 cells.(A) The Western Blot Image of time course of Phosphorylated ERK1/2 Expression in A549 Treated with 100 µM propofol. (B) The Quantification of the Western Blot. These results are representative of three independent experiments with a total of 15 samples. By using One Way ANOVA testing, we found the differences from all one-hour propofol groups to be significantly lower compared with the 0-hour group with a P value <0.0001. ANOVA was used to do the analysis.
Mentions: ERK is one of the key factors in the Ras/Raf/MEK/ERK signaling pathway. This pathway promotes cell proliferation, cell survival and metastasis. Usually it is aberrantly activated in cancer [17]. The activation of ERK is associated with K-Ras mutation in cancer cells [18]). We next sought to determine the activation of ERK1/2 in K-Ras mutant A549 cells after propofol treatment. We found that the phosphorylated ERK1/2, the activated form of ERK1/2, started to decrease at 60 minutes after propofol treatment and returned to the basal level at 5 hour time point (Fig. 3).

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