Limits...
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.

Show MeSH

Related in: MedlinePlus

High Content Analysis of caspase 3 expression in three cell lines.Propofol treatment induces apoptosis in A549 cells significantly, slightly induces apoptosis in LoVo cells, and no change in SKBR3 cells. (A) High content analysis of caspase-3 expression in A549 cells treated with the indicated propofol concentrations for 24 hours. Nuclei were stained with Hoechst 33342 shown in blue color. Caspase-3- positive stained cell are shown in green color. Images were acquired at 5× magnification lens. (a) A549 cells treated with 0.5% DMSO for 24 hours. (b) A549 cells treated with 25 µM of propofol in 0.5% DMSO for 24 hours. (c) A549 cells treated with 50 µM of propofol in 0.5% DMSO for 24 hours. (d) A549 cells treated with 100 µM of propofol in 0.5% DMSO for 24 hours. These results are representative of three independent experiments. (B) High Content analysis of caspase-3 expression in LoVo cells treated with indicated propofol concentrations for 24 hour. Nuclei were stained with Hoechst 33342 shown in blue color. Caspase-3 positive stained cells are shown in green color. Images were acquired at 5× magnification lens. (a) LoVo cells treated with 0.5% DMSO for 24 hours. (b) LoVo cells treated with 25 µM of propofol made with 0.5% DMSO for 24 hour. (c) LoVo cells treated with 50 µM of propofol made with 0.5% DMSO for 24 hour. (d) LoVo cells treated with 100 µM of propofol made with 0.5% DMSO for 24 hour. These results are representative of three independent experiments. (C) Charts indicating the caspase-3 expression in A549 cells (a), LoVo cells (b), and SKBR3 cells (c) with the administration of propofol for 24 hours. There is no change after 6 hour treatment with propofol for any of these three cell lines tested here (Data not shown). Each value was determined with Target Activation BioApplication Guide suggested by manufactory (Thermo Scientific), and normalized to the expression of cpaspase 3 with 0.5% DMSO incubation. The results were evaluated by ANOVA test. A star () indicates statistically significant with the P<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4263663&req=5

pone-0114440-g001: High Content Analysis of caspase 3 expression in three cell lines.Propofol treatment induces apoptosis in A549 cells significantly, slightly induces apoptosis in LoVo cells, and no change in SKBR3 cells. (A) High content analysis of caspase-3 expression in A549 cells treated with the indicated propofol concentrations for 24 hours. Nuclei were stained with Hoechst 33342 shown in blue color. Caspase-3- positive stained cell are shown in green color. Images were acquired at 5× magnification lens. (a) A549 cells treated with 0.5% DMSO for 24 hours. (b) A549 cells treated with 25 µM of propofol in 0.5% DMSO for 24 hours. (c) A549 cells treated with 50 µM of propofol in 0.5% DMSO for 24 hours. (d) A549 cells treated with 100 µM of propofol in 0.5% DMSO for 24 hours. These results are representative of three independent experiments. (B) High Content analysis of caspase-3 expression in LoVo cells treated with indicated propofol concentrations for 24 hour. Nuclei were stained with Hoechst 33342 shown in blue color. Caspase-3 positive stained cells are shown in green color. Images were acquired at 5× magnification lens. (a) LoVo cells treated with 0.5% DMSO for 24 hours. (b) LoVo cells treated with 25 µM of propofol made with 0.5% DMSO for 24 hour. (c) LoVo cells treated with 50 µM of propofol made with 0.5% DMSO for 24 hour. (d) LoVo cells treated with 100 µM of propofol made with 0.5% DMSO for 24 hour. These results are representative of three independent experiments. (C) Charts indicating the caspase-3 expression in A549 cells (a), LoVo cells (b), and SKBR3 cells (c) with the administration of propofol for 24 hours. There is no change after 6 hour treatment with propofol for any of these three cell lines tested here (Data not shown). Each value was determined with Target Activation BioApplication Guide suggested by manufactory (Thermo Scientific), and normalized to the expression of cpaspase 3 with 0.5% DMSO incubation. The results were evaluated by ANOVA test. A star () indicates statistically significant with the P<0.05.

Mentions: In caspase-mediated apoptotic pathways, there is an activation of a series of caspase family proteases. Caspase 3, a key destructive enzyme, is involved in both the death-receptor-mediated and mitochondria- dependent pathway [14]. To determine the effects of propofol on the induction of apoptosis for these three cell lines (A549, LoVo, and SKBR3), caspase-3 was selected as an apoptotic marker in our study. As shown in Fig. 1, caspase-3 was significantly more highly expressed in the A549 cell after 24-hours of 100 µM of propofol treatment, in a dose-dependent manner, compared with controls. In the LoVo cell, there was a trend toward high expression for caspase-3 after 24-hours treatment with 100 µM of propofol. Propofol had no such effect on SKBR3 cells.


Mini profile of potential anticancer properties of propofol.

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

High Content Analysis of caspase 3 expression in three cell lines.Propofol treatment induces apoptosis in A549 cells significantly, slightly induces apoptosis in LoVo cells, and no change in SKBR3 cells. (A) High content analysis of caspase-3 expression in A549 cells treated with the indicated propofol concentrations for 24 hours. Nuclei were stained with Hoechst 33342 shown in blue color. Caspase-3- positive stained cell are shown in green color. Images were acquired at 5× magnification lens. (a) A549 cells treated with 0.5% DMSO for 24 hours. (b) A549 cells treated with 25 µM of propofol in 0.5% DMSO for 24 hours. (c) A549 cells treated with 50 µM of propofol in 0.5% DMSO for 24 hours. (d) A549 cells treated with 100 µM of propofol in 0.5% DMSO for 24 hours. These results are representative of three independent experiments. (B) High Content analysis of caspase-3 expression in LoVo cells treated with indicated propofol concentrations for 24 hour. Nuclei were stained with Hoechst 33342 shown in blue color. Caspase-3 positive stained cells are shown in green color. Images were acquired at 5× magnification lens. (a) LoVo cells treated with 0.5% DMSO for 24 hours. (b) LoVo cells treated with 25 µM of propofol made with 0.5% DMSO for 24 hour. (c) LoVo cells treated with 50 µM of propofol made with 0.5% DMSO for 24 hour. (d) LoVo cells treated with 100 µM of propofol made with 0.5% DMSO for 24 hour. These results are representative of three independent experiments. (C) Charts indicating the caspase-3 expression in A549 cells (a), LoVo cells (b), and SKBR3 cells (c) with the administration of propofol for 24 hours. There is no change after 6 hour treatment with propofol for any of these three cell lines tested here (Data not shown). Each value was determined with Target Activation BioApplication Guide suggested by manufactory (Thermo Scientific), and normalized to the expression of cpaspase 3 with 0.5% DMSO incubation. The results were evaluated by ANOVA test. A star () indicates statistically significant with the P<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0114440-g001: High Content Analysis of caspase 3 expression in three cell lines.Propofol treatment induces apoptosis in A549 cells significantly, slightly induces apoptosis in LoVo cells, and no change in SKBR3 cells. (A) High content analysis of caspase-3 expression in A549 cells treated with the indicated propofol concentrations for 24 hours. Nuclei were stained with Hoechst 33342 shown in blue color. Caspase-3- positive stained cell are shown in green color. Images were acquired at 5× magnification lens. (a) A549 cells treated with 0.5% DMSO for 24 hours. (b) A549 cells treated with 25 µM of propofol in 0.5% DMSO for 24 hours. (c) A549 cells treated with 50 µM of propofol in 0.5% DMSO for 24 hours. (d) A549 cells treated with 100 µM of propofol in 0.5% DMSO for 24 hours. These results are representative of three independent experiments. (B) High Content analysis of caspase-3 expression in LoVo cells treated with indicated propofol concentrations for 24 hour. Nuclei were stained with Hoechst 33342 shown in blue color. Caspase-3 positive stained cells are shown in green color. Images were acquired at 5× magnification lens. (a) LoVo cells treated with 0.5% DMSO for 24 hours. (b) LoVo cells treated with 25 µM of propofol made with 0.5% DMSO for 24 hour. (c) LoVo cells treated with 50 µM of propofol made with 0.5% DMSO for 24 hour. (d) LoVo cells treated with 100 µM of propofol made with 0.5% DMSO for 24 hour. These results are representative of three independent experiments. (C) Charts indicating the caspase-3 expression in A549 cells (a), LoVo cells (b), and SKBR3 cells (c) with the administration of propofol for 24 hours. There is no change after 6 hour treatment with propofol for any of these three cell lines tested here (Data not shown). Each value was determined with Target Activation BioApplication Guide suggested by manufactory (Thermo Scientific), and normalized to the expression of cpaspase 3 with 0.5% DMSO incubation. The results were evaluated by ANOVA test. A star () indicates statistically significant with the P<0.05.
Mentions: In caspase-mediated apoptotic pathways, there is an activation of a series of caspase family proteases. Caspase 3, a key destructive enzyme, is involved in both the death-receptor-mediated and mitochondria- dependent pathway [14]. To determine the effects of propofol on the induction of apoptosis for these three cell lines (A549, LoVo, and SKBR3), caspase-3 was selected as an apoptotic marker in our study. As shown in Fig. 1, caspase-3 was significantly more highly expressed in the A549 cell after 24-hours of 100 µM of propofol treatment, in a dose-dependent manner, compared with controls. In the LoVo cell, there was a trend toward high expression for caspase-3 after 24-hours treatment with 100 µM of propofol. Propofol had no such effect on SKBR3 cells.

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