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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

Immunohistochemical results for p21 and p27.Various groups of mammary tumor were screen as: Tumor control (A), FALHE low-dose treatment (B), FALHE high-dose treatment (C), and tamoxifen treatment (D). Dark brown particles are indicating the expression of p21 and p27. High expression of p21 and p27 was observed after FALHE treatment compared with the tumor control, revealing cell cycle arrest.
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pone.0127434.g007: Immunohistochemical results for p21 and p27.Various groups of mammary tumor were screen as: Tumor control (A), FALHE low-dose treatment (B), FALHE high-dose treatment (C), and tamoxifen treatment (D). Dark brown particles are indicating the expression of p21 and p27. High expression of p21 and p27 was observed after FALHE treatment compared with the tumor control, revealing cell cycle arrest.

Mentions: The immunohistochemical results for the protein expression of Bax/Bcl-2 and caspase 3 showed an upregulation of Bax and caspase 3 and a downregulation of Bcl-2 after treatment with FALHE. Moreover, low expression levels of Bax and caspase 3 and a high expression level of Bcl-2 were observed in the cancer control group. These results showed an activation of the intrinsic pathway of apoptosis (Fig 6). Furthermore, p53, p21 and p27 play an essential role in the regulation of G1 phase arrest in cell cycle proliferation. The expression of these proteins was upregulated after FALHE treatment and downregulated in the cancer control group (Fig 7).


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)

Immunohistochemical results for p21 and p27.Various groups of mammary tumor were screen as: Tumor control (A), FALHE low-dose treatment (B), FALHE high-dose treatment (C), and tamoxifen treatment (D). Dark brown particles are indicating the expression of p21 and p27. High expression of p21 and p27 was observed after FALHE treatment compared with the tumor control, revealing cell cycle arrest.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0127434.g007: Immunohistochemical results for p21 and p27.Various groups of mammary tumor were screen as: Tumor control (A), FALHE low-dose treatment (B), FALHE high-dose treatment (C), and tamoxifen treatment (D). Dark brown particles are indicating the expression of p21 and p27. High expression of p21 and p27 was observed after FALHE treatment compared with the tumor control, revealing cell cycle arrest.
Mentions: The immunohistochemical results for the protein expression of Bax/Bcl-2 and caspase 3 showed an upregulation of Bax and caspase 3 and a downregulation of Bcl-2 after treatment with FALHE. Moreover, low expression levels of Bax and caspase 3 and a high expression level of Bcl-2 were observed in the cancer control group. These results showed an activation of the intrinsic pathway of apoptosis (Fig 6). Furthermore, p53, p21 and p27 play an essential role in the regulation of G1 phase arrest in cell cycle proliferation. The expression of these proteins was upregulated after FALHE treatment and downregulated in the cancer control group (Fig 7).

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