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A novel bifunctional mitochondria-targeted anticancer agent with high selectivity for cancer cells.

He H, Li DW, Yang LY, Fu L, Zhu XJ, Wong WK, Jiang FL, Liu Y - Sci Rep (2015)

Bottom Line: Herein, we demonstrate a novel bifunctional mitochondria-targeted anticancer agent (FPB), exhibiting both imaging capability and anticancer activity.It can selectively accumulate in mitochondria and induce cell apoptosis.These features make it highly attractive in cancer imaging and treatment.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Virology &Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry Molecular Sciences, Wuhan University, Wuhan 430072, P. R. China.

ABSTRACT
Mitochondria have recently emerged as novel targets for cancer therapy due to its important roles in fundamental cellular function. Discovery of new chemotherapeutic agents that allow for simultaneous treatment and visualization of cancer is urgent. Herein, we demonstrate a novel bifunctional mitochondria-targeted anticancer agent (FPB), exhibiting both imaging capability and anticancer activity. It can selectively accumulate in mitochondria and induce cell apoptosis. Notably, it results in much higher toxicity toward cancer cells owing to much higher uptake by cancer cells. These features make it highly attractive in cancer imaging and treatment.

No MeSH data available.


Related in: MedlinePlus

DNA fluorescence histograms of PI-stained SGC-7901 cells treated with FPB of different concentrations.The values in figure represented the percentage of apoptosis.
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f5: DNA fluorescence histograms of PI-stained SGC-7901 cells treated with FPB of different concentrations.The values in figure represented the percentage of apoptosis.

Mentions: To further study the anticancer mechanism of FPB, we performed apoptosis assay of SGC-7901 cells after incubation with FPB for 48 h by flow cytometry. Cells were stained with propidium (PI) dye for nucleic acid staining. Because the apoptotic cells are characterized by DNA fragmentation at the internucleosomal section and consequently loss of nuclear DNA content, they display a broad hypodiploid (sub-G1) peak after stained with PI and analysed with flow cytometer30. As shown in Fig. 5, flow cytomeric analysis of PI-stained apoptotic cells shows a distinctive broad peak of hypodiploid particles, clearly different from the diploid DNA peak of normal cells. The proportion of apoptotic cells increased in a dose-dependent manner. At 10 μM of FPB, the percentage of apoptotic cells is over 50% (Fig. 5d). Moreover, contrast cell volume behaviours (swelling vs. shrinkage) are considered as important markers to identify apoptosis and necrosis31. Thus laser light scatter characteristics of cell morphology could also be used to reflect cell apoptosis32. Markedly decrease in intensity of forward light scatter (FSC) signal and increase in intensity of side scatter (SSC) signal were observed for cells after treated with FPB (Fig. S6 (SI)), reflecting the cell volume shrinkage and condensation of nucleus and cytoplasm, which is a typical morphological feature of apoptotic cells. The reduction in cell volume is also illustrated in direct phase contrast images (Fig. 2c,d). Combining the DNA fragmentation and cell morphological features, we concluded that FPB could effectively induce cell apoptosis to kill cancer cells.


A novel bifunctional mitochondria-targeted anticancer agent with high selectivity for cancer cells.

He H, Li DW, Yang LY, Fu L, Zhu XJ, Wong WK, Jiang FL, Liu Y - Sci Rep (2015)

DNA fluorescence histograms of PI-stained SGC-7901 cells treated with FPB of different concentrations.The values in figure represented the percentage of apoptosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4559806&req=5

f5: DNA fluorescence histograms of PI-stained SGC-7901 cells treated with FPB of different concentrations.The values in figure represented the percentage of apoptosis.
Mentions: To further study the anticancer mechanism of FPB, we performed apoptosis assay of SGC-7901 cells after incubation with FPB for 48 h by flow cytometry. Cells were stained with propidium (PI) dye for nucleic acid staining. Because the apoptotic cells are characterized by DNA fragmentation at the internucleosomal section and consequently loss of nuclear DNA content, they display a broad hypodiploid (sub-G1) peak after stained with PI and analysed with flow cytometer30. As shown in Fig. 5, flow cytomeric analysis of PI-stained apoptotic cells shows a distinctive broad peak of hypodiploid particles, clearly different from the diploid DNA peak of normal cells. The proportion of apoptotic cells increased in a dose-dependent manner. At 10 μM of FPB, the percentage of apoptotic cells is over 50% (Fig. 5d). Moreover, contrast cell volume behaviours (swelling vs. shrinkage) are considered as important markers to identify apoptosis and necrosis31. Thus laser light scatter characteristics of cell morphology could also be used to reflect cell apoptosis32. Markedly decrease in intensity of forward light scatter (FSC) signal and increase in intensity of side scatter (SSC) signal were observed for cells after treated with FPB (Fig. S6 (SI)), reflecting the cell volume shrinkage and condensation of nucleus and cytoplasm, which is a typical morphological feature of apoptotic cells. The reduction in cell volume is also illustrated in direct phase contrast images (Fig. 2c,d). Combining the DNA fragmentation and cell morphological features, we concluded that FPB could effectively induce cell apoptosis to kill cancer cells.

Bottom Line: Herein, we demonstrate a novel bifunctional mitochondria-targeted anticancer agent (FPB), exhibiting both imaging capability and anticancer activity.It can selectively accumulate in mitochondria and induce cell apoptosis.These features make it highly attractive in cancer imaging and treatment.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Virology &Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry Molecular Sciences, Wuhan University, Wuhan 430072, P. R. China.

ABSTRACT
Mitochondria have recently emerged as novel targets for cancer therapy due to its important roles in fundamental cellular function. Discovery of new chemotherapeutic agents that allow for simultaneous treatment and visualization of cancer is urgent. Herein, we demonstrate a novel bifunctional mitochondria-targeted anticancer agent (FPB), exhibiting both imaging capability and anticancer activity. It can selectively accumulate in mitochondria and induce cell apoptosis. Notably, it results in much higher toxicity toward cancer cells owing to much higher uptake by cancer cells. These features make it highly attractive in cancer imaging and treatment.

No MeSH data available.


Related in: MedlinePlus