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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

(a) IC50 values of FPB for different cell lines. (b) Cell viability of SGC-7901 treated with FPB, F16-Ph-Ace, and BODIPY-I using a typical MTT assay. (c) Phase contrast images of SGC-7901 cell lines treated without FPB for 48 h. (d) Phase contrast images of SGC-7901 cell lines treated with FPB (5 μM) for 48 h.
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f2: (a) IC50 values of FPB for different cell lines. (b) Cell viability of SGC-7901 treated with FPB, F16-Ph-Ace, and BODIPY-I using a typical MTT assay. (c) Phase contrast images of SGC-7901 cell lines treated without FPB for 48 h. (d) Phase contrast images of SGC-7901 cell lines treated with FPB (5 μM) for 48 h.

Mentions: The cytotoxicity of FPB was first studied by the typical MTT [3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide] method. Three normal cell lines, human gastric mucosal epithelial cell lines (GES-1), human embryonic kidney 293 cell lines (HEK293) and mouse fibroblast cell lines (NIH/3T3), and three cancer cell lines, gastric cancer cell lines (SGC-7901), pulmonary adenocarcinoma cell lines (A549) and human breast adenocarcinoma cell lines (MCF-7) were used as target cells. The cytotoxicity data of FPB toward the six different cells are provided in Fig. S5 (SI) and the IC50 values were calculated as shown in Fig. 2a. Noteworthy, FPB shows different toxic effects towards carcinoma and normal cell lines. All carcinoma cell lines (SGC-7901, MCF-7 and A549) are sensitive to FPB with the IC50 in the range of 2.49 μM to 6.20 μM, while two normal cell lines (GES-1 and HEK293) are less sensitive to FPB with the IC50 of 16.4 μM and 12.2 μM. Especially for SGC-7901 and GES-1, the human gastric carcinoma cells and corresponding normal cells, the selective factor (ratio of IC50) is about 6.58. GES-1 and HEK293 cells are not strictly normal cells as they are transformed with SV40 or Ad5 virus, so we further tested the toxicity of FPB on the normal fibroblast cells. The results indicated that the toxicity of FPB on 3T3 cells is lower compared with GES-1 and HEK293. The phase contrast images of SGC-7901 cells were also taken before and after incubating with 5 μM FPB for 48 h. As shown in Fig. 2c,d, the cell volume of SGC-7901 cells treated with FPB were obviously smaller than that without FPB. The reduced cell size and abnormal cellular morphology indicated that the cells were dead or in the late stage of apoptosis. This result is consistent with the MTT experiment. These results demonstrate that FPB can act as an anticancer agent of broad spectrum and exhibits good selectivity to cancerous cell lines over normal cell lines.


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)

(a) IC50 values of FPB for different cell lines. (b) Cell viability of SGC-7901 treated with FPB, F16-Ph-Ace, and BODIPY-I using a typical MTT assay. (c) Phase contrast images of SGC-7901 cell lines treated without FPB for 48 h. (d) Phase contrast images of SGC-7901 cell lines treated with FPB (5 μM) for 48 h.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: (a) IC50 values of FPB for different cell lines. (b) Cell viability of SGC-7901 treated with FPB, F16-Ph-Ace, and BODIPY-I using a typical MTT assay. (c) Phase contrast images of SGC-7901 cell lines treated without FPB for 48 h. (d) Phase contrast images of SGC-7901 cell lines treated with FPB (5 μM) for 48 h.
Mentions: The cytotoxicity of FPB was first studied by the typical MTT [3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide] method. Three normal cell lines, human gastric mucosal epithelial cell lines (GES-1), human embryonic kidney 293 cell lines (HEK293) and mouse fibroblast cell lines (NIH/3T3), and three cancer cell lines, gastric cancer cell lines (SGC-7901), pulmonary adenocarcinoma cell lines (A549) and human breast adenocarcinoma cell lines (MCF-7) were used as target cells. The cytotoxicity data of FPB toward the six different cells are provided in Fig. S5 (SI) and the IC50 values were calculated as shown in Fig. 2a. Noteworthy, FPB shows different toxic effects towards carcinoma and normal cell lines. All carcinoma cell lines (SGC-7901, MCF-7 and A549) are sensitive to FPB with the IC50 in the range of 2.49 μM to 6.20 μM, while two normal cell lines (GES-1 and HEK293) are less sensitive to FPB with the IC50 of 16.4 μM and 12.2 μM. Especially for SGC-7901 and GES-1, the human gastric carcinoma cells and corresponding normal cells, the selective factor (ratio of IC50) is about 6.58. GES-1 and HEK293 cells are not strictly normal cells as they are transformed with SV40 or Ad5 virus, so we further tested the toxicity of FPB on the normal fibroblast cells. The results indicated that the toxicity of FPB on 3T3 cells is lower compared with GES-1 and HEK293. The phase contrast images of SGC-7901 cells were also taken before and after incubating with 5 μM FPB for 48 h. As shown in Fig. 2c,d, the cell volume of SGC-7901 cells treated with FPB were obviously smaller than that without FPB. The reduced cell size and abnormal cellular morphology indicated that the cells were dead or in the late stage of apoptosis. This result is consistent with the MTT experiment. These results demonstrate that FPB can act as an anticancer agent of broad spectrum and exhibits good selectivity to cancerous cell lines over normal cell lines.

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