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Polyphenol-rich extract of Salvia chinensis exhibits anticancer activity in different cancer cell lines, and induces cell cycle arrest at the G₀/G₁-phase, apoptosis and loss of mitochondrial membrane potential in pancreatic cancer cells.

Zhao Q, Huo XC, Sun FD, Dong RQ - Mol Med Rep (2015)

Bottom Line: PC is the fourth most common cause of cancer‑associated mortality in the western world.At present, there is almost no effective treatment available for the treatment of PC.In addition, treatment with the extract induced a significant and concentration-dependent reduction in the ΛΨm of the PC cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.

ABSTRACT
Pancreatic cancer (PC) is one of the most aggressive types of human malignancy, which has an overall 5-year survival rate of <2%. PC is the fourth most common cause of cancer‑associated mortality in the western world. At present, there is almost no effective treatment available for the treatment of PC. The aim of the present study was to evaluate the anticancer potential of a polyphenol enriched extract obtained from Salvia chinensis, a Chinese medicinal plant. An MTT assay was used to evaluate the cell viability of five cancer cell lines and one normal cell line. In addition, the effects of the extract on apoptotic induction, cell cycle phase distribution, DNA damage and loss of mitochondrial membrane potential (ΛΨm) were evaluated in MiapaCa‑2 human PC cells. The effects of the extract on cell cycle phase distribution and ΛΨm were assessed by flow cytometry, using propidium iodide and rhodamine‑123 DNA‑binding fluorescent dyes, respectively. Fluorescence microscopy, using 4',6‑diamidino‑2‑phenylindole as a staining agent, was performed in order to detect the morphological changes of the MiapaCa‑2 cancer cells and the presence of apoptotic bodies following treatment with the extract. The results of the present study demonstrated that the polyphenol‑rich extract from S. chinensis induced potent cytotoxicity in the MCF‑7 human breast cancer cells, A549 human lung cancer cells, HCT‑116 and COLO 205 human colon cancer cells, and MiapaCa‑2 human PC cells. The Colo 205 and MCF‑7 cancer cell lines were the most susceptible to treatment with the extract, which exhibited increased rate of growth inhibition. Fluorescence microscopy revealed characteristic morphological features of apoptosis and detected the appearance of apoptotic bodies following treatment with the extract in the PC cells. Flow cytometric analysis demonstrated that the extract induced G0/G1 cell cycle arrest in a dose‑dependent manner. In addition, treatment with the extract induced a significant and concentration-dependent reduction in the ΛΨm of the PC cells.

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Effects of different concentrations of polyphenol-rich extract of Salvia chinensis on the cell cycle distribution of MiapaCa-2 human pancreatic cancer cells, determined using flow cytometry. The effects of (A) 20, (B) 40, (C) 60 and (D) 80 µg/ml of the extract on the cells are shown. The corresponding pie charts indicate the percentage increase in the G0/G1 cell populations with increasing extract concentration.
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f5-mmr-12-04-4843: Effects of different concentrations of polyphenol-rich extract of Salvia chinensis on the cell cycle distribution of MiapaCa-2 human pancreatic cancer cells, determined using flow cytometry. The effects of (A) 20, (B) 40, (C) 60 and (D) 80 µg/ml of the extract on the cells are shown. The corresponding pie charts indicate the percentage increase in the G0/G1 cell populations with increasing extract concentration.

Mentions: Apoptosis and cell cycle dysfunction are closely associated biochemical processes, and any disturbance in cell cycle progression may lead to apoptotic cell death (35). In order to determine the mechanism underlying the growth inhibitory effect of the extract on MiapaCa-2 cancer cells, flow cytometric analysis was performed to detect whether the extract induced cell cycle arrest. Treatment with different concentrations of the extract for 48 h induced G0/G1-phase growth arrest in the MiapaCa-2 cells. As shown in Fig. 5, following treatment of the MiapaCa-2 cells with different concentrations of the extract (20, 40, 60 and 80 µg/ml), considerable G0/G1 cell cycle growth arrest was observed. The apoptotic cells were observed as shrunken cells with degraded chromatin, increased side scatter and decreased forward scatter properties. The increase in the sub-G1 cell population (hypodiploid DNA content) may be due to DNA fragmentation, which eventually results in apoptotic cell death. Inhibition of cell cycle progression may be one of the molecular events associated with the cytotoxic activities of the extract. Following treatment of the cells with low concentrations of the extract, no significant differences were observed in the levels of apoptosis; however, following treatment with extract concentrations of 60 and 80 µg/ml, the percentage of cells undergoing apoptosis (G0/G1 arrest) increased significantly.


Polyphenol-rich extract of Salvia chinensis exhibits anticancer activity in different cancer cell lines, and induces cell cycle arrest at the G₀/G₁-phase, apoptosis and loss of mitochondrial membrane potential in pancreatic cancer cells.

Zhao Q, Huo XC, Sun FD, Dong RQ - Mol Med Rep (2015)

Effects of different concentrations of polyphenol-rich extract of Salvia chinensis on the cell cycle distribution of MiapaCa-2 human pancreatic cancer cells, determined using flow cytometry. The effects of (A) 20, (B) 40, (C) 60 and (D) 80 µg/ml of the extract on the cells are shown. The corresponding pie charts indicate the percentage increase in the G0/G1 cell populations with increasing extract concentration.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581742&req=5

f5-mmr-12-04-4843: Effects of different concentrations of polyphenol-rich extract of Salvia chinensis on the cell cycle distribution of MiapaCa-2 human pancreatic cancer cells, determined using flow cytometry. The effects of (A) 20, (B) 40, (C) 60 and (D) 80 µg/ml of the extract on the cells are shown. The corresponding pie charts indicate the percentage increase in the G0/G1 cell populations with increasing extract concentration.
Mentions: Apoptosis and cell cycle dysfunction are closely associated biochemical processes, and any disturbance in cell cycle progression may lead to apoptotic cell death (35). In order to determine the mechanism underlying the growth inhibitory effect of the extract on MiapaCa-2 cancer cells, flow cytometric analysis was performed to detect whether the extract induced cell cycle arrest. Treatment with different concentrations of the extract for 48 h induced G0/G1-phase growth arrest in the MiapaCa-2 cells. As shown in Fig. 5, following treatment of the MiapaCa-2 cells with different concentrations of the extract (20, 40, 60 and 80 µg/ml), considerable G0/G1 cell cycle growth arrest was observed. The apoptotic cells were observed as shrunken cells with degraded chromatin, increased side scatter and decreased forward scatter properties. The increase in the sub-G1 cell population (hypodiploid DNA content) may be due to DNA fragmentation, which eventually results in apoptotic cell death. Inhibition of cell cycle progression may be one of the molecular events associated with the cytotoxic activities of the extract. Following treatment of the cells with low concentrations of the extract, no significant differences were observed in the levels of apoptosis; however, following treatment with extract concentrations of 60 and 80 µg/ml, the percentage of cells undergoing apoptosis (G0/G1 arrest) increased significantly.

Bottom Line: PC is the fourth most common cause of cancer‑associated mortality in the western world.At present, there is almost no effective treatment available for the treatment of PC.In addition, treatment with the extract induced a significant and concentration-dependent reduction in the ΛΨm of the PC cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.

ABSTRACT
Pancreatic cancer (PC) is one of the most aggressive types of human malignancy, which has an overall 5-year survival rate of <2%. PC is the fourth most common cause of cancer‑associated mortality in the western world. At present, there is almost no effective treatment available for the treatment of PC. The aim of the present study was to evaluate the anticancer potential of a polyphenol enriched extract obtained from Salvia chinensis, a Chinese medicinal plant. An MTT assay was used to evaluate the cell viability of five cancer cell lines and one normal cell line. In addition, the effects of the extract on apoptotic induction, cell cycle phase distribution, DNA damage and loss of mitochondrial membrane potential (ΛΨm) were evaluated in MiapaCa‑2 human PC cells. The effects of the extract on cell cycle phase distribution and ΛΨm were assessed by flow cytometry, using propidium iodide and rhodamine‑123 DNA‑binding fluorescent dyes, respectively. Fluorescence microscopy, using 4',6‑diamidino‑2‑phenylindole as a staining agent, was performed in order to detect the morphological changes of the MiapaCa‑2 cancer cells and the presence of apoptotic bodies following treatment with the extract. The results of the present study demonstrated that the polyphenol‑rich extract from S. chinensis induced potent cytotoxicity in the MCF‑7 human breast cancer cells, A549 human lung cancer cells, HCT‑116 and COLO 205 human colon cancer cells, and MiapaCa‑2 human PC cells. The Colo 205 and MCF‑7 cancer cell lines were the most susceptible to treatment with the extract, which exhibited increased rate of growth inhibition. Fluorescence microscopy revealed characteristic morphological features of apoptosis and detected the appearance of apoptotic bodies following treatment with the extract in the PC cells. Flow cytometric analysis demonstrated that the extract induced G0/G1 cell cycle arrest in a dose‑dependent manner. In addition, treatment with the extract induced a significant and concentration-dependent reduction in the ΛΨm of the PC cells.

Show MeSH
Related in: MedlinePlus