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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 the polyphenol-rich extract of Salvia chinensis on the loss of mitochondrial membrane potential in MiapaCa-2 human pancreatic cancer cells. (A) Camptothecin-treated cells (positive control) and cells treated with (B) 20, (C) 40, (D) 60 and (E) 80 µg/ml of the extract.
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f6-mmr-12-04-4843: Effects of different concentrations of the polyphenol-rich extract of Salvia chinensis on the loss of mitochondrial membrane potential in MiapaCa-2 human pancreatic cancer cells. (A) Camptothecin-treated cells (positive control) and cells treated with (B) 20, (C) 40, (D) 60 and (E) 80 µg/ml of the extract.

Mentions: Depolarization of the mitochondrial membrane and subsequent seepage of the outer membrane is a key step in the intrinsic apoptotic pathway. This is usually followed by the release of cytochrome c and pro-apoptotic molecules (36). The present study used the fluorescent probe, Rh-123, to detect the ΛΨm in living cells. Treatment with the extract induced a substantial reduction in the number of cells with intact membrane potential, and increased the number of cells with a low ΛΨm after 48 h (Fig. 6). Loss of ΛΨm is a crucial event in the mitochondrial apoptotic pathway. The loss of ΛΨm was found to exhibit dose-dependence, and the number of cells with reduced ΛΨm increased with increasing concentrations of the extract.


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 the polyphenol-rich extract of Salvia chinensis on the loss of mitochondrial membrane potential in MiapaCa-2 human pancreatic cancer cells. (A) Camptothecin-treated cells (positive control) and cells treated with (B) 20, (C) 40, (D) 60 and (E) 80 µg/ml of the extract.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6-mmr-12-04-4843: Effects of different concentrations of the polyphenol-rich extract of Salvia chinensis on the loss of mitochondrial membrane potential in MiapaCa-2 human pancreatic cancer cells. (A) Camptothecin-treated cells (positive control) and cells treated with (B) 20, (C) 40, (D) 60 and (E) 80 µg/ml of the extract.
Mentions: Depolarization of the mitochondrial membrane and subsequent seepage of the outer membrane is a key step in the intrinsic apoptotic pathway. This is usually followed by the release of cytochrome c and pro-apoptotic molecules (36). The present study used the fluorescent probe, Rh-123, to detect the ΛΨm in living cells. Treatment with the extract induced a substantial reduction in the number of cells with intact membrane potential, and increased the number of cells with a low ΛΨm after 48 h (Fig. 6). Loss of ΛΨm is a crucial event in the mitochondrial apoptotic pathway. The loss of ΛΨm was found to exhibit dose-dependence, and the number of cells with reduced ΛΨm increased with increasing concentrations of the extract.

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