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Chemopreventive Activity of Ferulago angulate against Breast Tumor in Rats and the Apoptotic Effect of Polycerasoidin in MCF7 Cells: A Bioassay-Guided Approach.

Karimian H, Fadaeinasab M, Zorofchian Moghadamtousi S, Hajrezaei M, Razavi M, Safi SZ, Ameen Abdulla M, Mohd Ali H, Ibrahim Noordin M - PLoS ONE (2015)

Bottom Line: Ferulago angulata leaf hexane extract (FALHE) was found to be a potent inducer of MCF7 cell apoptosis.In addition, flow cytometric analysis demonstrated that the treated MCF7 cells were arrested at the G1 phase, and this was associated with the up-regulation of p21 and p27 at both the mRNA and protein levels.The results of the present study reinforce further investigations scrutinizing the promising potential of the F. angulata chemical constituents as breast cancer chemopreventive agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

ABSTRACT
Ferulago angulata leaf hexane extract (FALHE) was found to be a potent inducer of MCF7 cell apoptosis. The aims of the present study were to investigate the in vivo chemopreventive effect of FALHE in rats, to identify the contributing anticancer compound in FALHE and to determine its potential mechanism of action against MCF7 cells. Thirty rats harboring LA7-induced breast tumors were divided into five groups: tumor control, low-dose FALHE, high-dose FALHE, treatment control (tamoxifen) and normal control. Breast tissues were then subjected to histopathological and immunohistochemical analyses. A bioassay-guided investigation on FALHE was performed to identify the cytotoxic compound and its mechanism of action through flow cytometry, real-time qPCR and western blotting analyses. An in vivo study showed that FALHE suppressed the expression of the tumor markers PCNA and Ki67. The tumor size was reduced from 2031 ± 281 mm3 to 432 ± 201 mm3 after FALHE treatment. FALHE administration induced apoptosis in breast tumor cells, and this was confirmed by high expression levels of Bax, p53 and caspase 3. Cell cycle arrest was suggested by the expression of p21 and p27. The in vitro experimental results resulted in the isolation of polycerasoidin as a bioactive ingredient of FALHE with an IC50 value of 3.16 ± 0.31 μg/ml against MCF7 cells. Polycerasoidin induced mitochondrial-dependent apoptosis in breast cancer cells via caspase activation and changes in the mRNA and protein expression of Bax and Bcl-2. In addition, flow cytometric analysis demonstrated that the treated MCF7 cells were arrested at the G1 phase, and this was associated with the up-regulation of p21 and p27 at both the mRNA and protein levels. The results of the present study reinforce further investigations scrutinizing the promising potential of the F. angulata chemical constituents as breast cancer chemopreventive agents.

No MeSH data available.


Related in: MedlinePlus

Cell cycle distribution in polycerasoidin-treated MCF7 cells.(A) 0.1% DMSO treatment for 48 h was used as a vehicle control. The percentage of IC50 concentration of polycerasoidin-treated cells at the G0/G1, S and G2/M phases was examined after (B) 12, (C) 24 and (D) 48 h. (E) Analysis of the cell cycle distribution showed increase in G1 population which revealed time-dependent cell cycle arrest at the G0/G1 phase. The data are shown as the means ± SEM. Values are statistically significant at *P<0.05.
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pone.0127434.g008: Cell cycle distribution in polycerasoidin-treated MCF7 cells.(A) 0.1% DMSO treatment for 48 h was used as a vehicle control. The percentage of IC50 concentration of polycerasoidin-treated cells at the G0/G1, S and G2/M phases was examined after (B) 12, (C) 24 and (D) 48 h. (E) Analysis of the cell cycle distribution showed increase in G1 population which revealed time-dependent cell cycle arrest at the G0/G1 phase. The data are shown as the means ± SEM. Values are statistically significant at *P<0.05.

Mentions: To determine whether the polycerasoidin anti-proliferative effect against MCF7 cells may be related to cell cycle arrest, cell cycle analysis was performed using flow cytometry. The cell cycle distribution was analyzed using a PI fluorescent dye, and the intensity represented the DNA content of each of the treated cells. As shown in Fig 8, a significant accumulation of cell distribution at the G1 phase was monitored after 12 h of treatment with polycerasoidin, and this accumulation was elevated by 66% and 69% after 24- and 48-h incubation periods, respectively. However, this increase was accompanied by a decreased accumulation of MCF7 cells at the S and G2/M phases after 48 h. Taken together, these findings revealed that cell cycle arrest is one of the contributing factors to the cytotoxic effect of polycerasoidin.


Chemopreventive Activity of Ferulago angulate against Breast Tumor in Rats and the Apoptotic Effect of Polycerasoidin in MCF7 Cells: A Bioassay-Guided Approach.

Karimian H, Fadaeinasab M, Zorofchian Moghadamtousi S, Hajrezaei M, Razavi M, Safi SZ, Ameen Abdulla M, Mohd Ali H, Ibrahim Noordin M - PLoS ONE (2015)

Cell cycle distribution in polycerasoidin-treated MCF7 cells.(A) 0.1% DMSO treatment for 48 h was used as a vehicle control. The percentage of IC50 concentration of polycerasoidin-treated cells at the G0/G1, S and G2/M phases was examined after (B) 12, (C) 24 and (D) 48 h. (E) Analysis of the cell cycle distribution showed increase in G1 population which revealed time-dependent cell cycle arrest at the G0/G1 phase. The data are shown as the means ± SEM. Values are statistically significant at *P<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4440818&req=5

pone.0127434.g008: Cell cycle distribution in polycerasoidin-treated MCF7 cells.(A) 0.1% DMSO treatment for 48 h was used as a vehicle control. The percentage of IC50 concentration of polycerasoidin-treated cells at the G0/G1, S and G2/M phases was examined after (B) 12, (C) 24 and (D) 48 h. (E) Analysis of the cell cycle distribution showed increase in G1 population which revealed time-dependent cell cycle arrest at the G0/G1 phase. The data are shown as the means ± SEM. Values are statistically significant at *P<0.05.
Mentions: To determine whether the polycerasoidin anti-proliferative effect against MCF7 cells may be related to cell cycle arrest, cell cycle analysis was performed using flow cytometry. The cell cycle distribution was analyzed using a PI fluorescent dye, and the intensity represented the DNA content of each of the treated cells. As shown in Fig 8, a significant accumulation of cell distribution at the G1 phase was monitored after 12 h of treatment with polycerasoidin, and this accumulation was elevated by 66% and 69% after 24- and 48-h incubation periods, respectively. However, this increase was accompanied by a decreased accumulation of MCF7 cells at the S and G2/M phases after 48 h. Taken together, these findings revealed that cell cycle arrest is one of the contributing factors to the cytotoxic effect of polycerasoidin.

Bottom Line: Ferulago angulata leaf hexane extract (FALHE) was found to be a potent inducer of MCF7 cell apoptosis.In addition, flow cytometric analysis demonstrated that the treated MCF7 cells were arrested at the G1 phase, and this was associated with the up-regulation of p21 and p27 at both the mRNA and protein levels.The results of the present study reinforce further investigations scrutinizing the promising potential of the F. angulata chemical constituents as breast cancer chemopreventive agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

ABSTRACT
Ferulago angulata leaf hexane extract (FALHE) was found to be a potent inducer of MCF7 cell apoptosis. The aims of the present study were to investigate the in vivo chemopreventive effect of FALHE in rats, to identify the contributing anticancer compound in FALHE and to determine its potential mechanism of action against MCF7 cells. Thirty rats harboring LA7-induced breast tumors were divided into five groups: tumor control, low-dose FALHE, high-dose FALHE, treatment control (tamoxifen) and normal control. Breast tissues were then subjected to histopathological and immunohistochemical analyses. A bioassay-guided investigation on FALHE was performed to identify the cytotoxic compound and its mechanism of action through flow cytometry, real-time qPCR and western blotting analyses. An in vivo study showed that FALHE suppressed the expression of the tumor markers PCNA and Ki67. The tumor size was reduced from 2031 ± 281 mm3 to 432 ± 201 mm3 after FALHE treatment. FALHE administration induced apoptosis in breast tumor cells, and this was confirmed by high expression levels of Bax, p53 and caspase 3. Cell cycle arrest was suggested by the expression of p21 and p27. The in vitro experimental results resulted in the isolation of polycerasoidin as a bioactive ingredient of FALHE with an IC50 value of 3.16 ± 0.31 μg/ml against MCF7 cells. Polycerasoidin induced mitochondrial-dependent apoptosis in breast cancer cells via caspase activation and changes in the mRNA and protein expression of Bax and Bcl-2. In addition, flow cytometric analysis demonstrated that the treated MCF7 cells were arrested at the G1 phase, and this was associated with the up-regulation of p21 and p27 at both the mRNA and protein levels. The results of the present study reinforce further investigations scrutinizing the promising potential of the F. angulata chemical constituents as breast cancer chemopreventive agents.

No MeSH data available.


Related in: MedlinePlus