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A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation.

Shi HS, Gao X, Li D, Zhang QW, Wang YS, Zheng Y, Cai LL, Zhong RM, Rui A, Li ZY, Zheng H, Chen XC, Chen LJ - Int J Nanomedicine (2012)

Bottom Line: The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model.The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation.This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, People's Republic of China.

ABSTRACT
Radiation pneumonitis (RP) is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomal curcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-κB pathway and downregulated inflammatory factors including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and transforming growth factor-β induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation. This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application.

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Lipo-cur sensitizes cancer cells to RT. (A and B) C57BL/6J mouse tumor model was established by subcutaneous injection with 5 × 105 LL/2 cells. Mice (six mice in each group) were treated with 100 μg of Lipo-cur (▲) (intravenous route), RT (⋄), Lipo-cur (intravenous route) and RT (■), or Lipo solution alone (●). Significant difference was found in tumor volume (*denotes P < 0.05) between RT-curcumin group and those two methods alone. Points, mean (n = 8); bars, standard deviation. (C and D) Apoptosis of lung cancer cells was detected using TUNEL analysis. The percentage of apoptosis was determined by counting the number of apoptotic cells and dividing by the total number of cells in the field (five high power fields per slide).Notes: The combined treatment with Lipo-cur and RT resulted in significantly increased apoptosis compared with that of other groups (*denotes P < 0.05, **denotes P < 0.01); bars, standard deviation; columns, mean.Abbreviations: Lipo, empty liposome; Lipo-cur, liposomal curcumin; RT, radiotherapy; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.
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f6-ijn-7-2601: Lipo-cur sensitizes cancer cells to RT. (A and B) C57BL/6J mouse tumor model was established by subcutaneous injection with 5 × 105 LL/2 cells. Mice (six mice in each group) were treated with 100 μg of Lipo-cur (▲) (intravenous route), RT (⋄), Lipo-cur (intravenous route) and RT (■), or Lipo solution alone (●). Significant difference was found in tumor volume (*denotes P < 0.05) between RT-curcumin group and those two methods alone. Points, mean (n = 8); bars, standard deviation. (C and D) Apoptosis of lung cancer cells was detected using TUNEL analysis. The percentage of apoptosis was determined by counting the number of apoptotic cells and dividing by the total number of cells in the field (five high power fields per slide).Notes: The combined treatment with Lipo-cur and RT resulted in significantly increased apoptosis compared with that of other groups (*denotes P < 0.05, **denotes P < 0.01); bars, standard deviation; columns, mean.Abbreviations: Lipo, empty liposome; Lipo-cur, liposomal curcumin; RT, radiotherapy; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.

Mentions: It has been reported that curcumin sensitizes human colorectal cancer xenografts in nude mice to gamma-radiation by targeting NF-κB-regulated gene products. The sensitizing effects of curcumin on murine lung cancer cells were investigated in LL/2 Lewis lung carcinoma cell model. There was significant inhibition of tumor growth in mice treated with curcumin plus radiotherapy. Although the antitumor effects were also detected in mice treated with curcumin and radiotherapy separately, the data suggest that the combined treatment of curcumin and radiotherapy can elicit an enhanced antitumor effect (Figure 6A and B). The further data from terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test also revealed curcumin plus radiotherapy induced significantly increased cellular apoptosis (Figure 6C and D). Therefore, the data suggest that Lipo-cur not only inhibit the process of RP, but also sensitize the antitumor effect of irradiation.


A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation.

Shi HS, Gao X, Li D, Zhang QW, Wang YS, Zheng Y, Cai LL, Zhong RM, Rui A, Li ZY, Zheng H, Chen XC, Chen LJ - Int J Nanomedicine (2012)

Lipo-cur sensitizes cancer cells to RT. (A and B) C57BL/6J mouse tumor model was established by subcutaneous injection with 5 × 105 LL/2 cells. Mice (six mice in each group) were treated with 100 μg of Lipo-cur (▲) (intravenous route), RT (⋄), Lipo-cur (intravenous route) and RT (■), or Lipo solution alone (●). Significant difference was found in tumor volume (*denotes P < 0.05) between RT-curcumin group and those two methods alone. Points, mean (n = 8); bars, standard deviation. (C and D) Apoptosis of lung cancer cells was detected using TUNEL analysis. The percentage of apoptosis was determined by counting the number of apoptotic cells and dividing by the total number of cells in the field (five high power fields per slide).Notes: The combined treatment with Lipo-cur and RT resulted in significantly increased apoptosis compared with that of other groups (*denotes P < 0.05, **denotes P < 0.01); bars, standard deviation; columns, mean.Abbreviations: Lipo, empty liposome; Lipo-cur, liposomal curcumin; RT, radiotherapy; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368513&req=5

f6-ijn-7-2601: Lipo-cur sensitizes cancer cells to RT. (A and B) C57BL/6J mouse tumor model was established by subcutaneous injection with 5 × 105 LL/2 cells. Mice (six mice in each group) were treated with 100 μg of Lipo-cur (▲) (intravenous route), RT (⋄), Lipo-cur (intravenous route) and RT (■), or Lipo solution alone (●). Significant difference was found in tumor volume (*denotes P < 0.05) between RT-curcumin group and those two methods alone. Points, mean (n = 8); bars, standard deviation. (C and D) Apoptosis of lung cancer cells was detected using TUNEL analysis. The percentage of apoptosis was determined by counting the number of apoptotic cells and dividing by the total number of cells in the field (five high power fields per slide).Notes: The combined treatment with Lipo-cur and RT resulted in significantly increased apoptosis compared with that of other groups (*denotes P < 0.05, **denotes P < 0.01); bars, standard deviation; columns, mean.Abbreviations: Lipo, empty liposome; Lipo-cur, liposomal curcumin; RT, radiotherapy; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.
Mentions: It has been reported that curcumin sensitizes human colorectal cancer xenografts in nude mice to gamma-radiation by targeting NF-κB-regulated gene products. The sensitizing effects of curcumin on murine lung cancer cells were investigated in LL/2 Lewis lung carcinoma cell model. There was significant inhibition of tumor growth in mice treated with curcumin plus radiotherapy. Although the antitumor effects were also detected in mice treated with curcumin and radiotherapy separately, the data suggest that the combined treatment of curcumin and radiotherapy can elicit an enhanced antitumor effect (Figure 6A and B). The further data from terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test also revealed curcumin plus radiotherapy induced significantly increased cellular apoptosis (Figure 6C and D). Therefore, the data suggest that Lipo-cur not only inhibit the process of RP, but also sensitize the antitumor effect of irradiation.

Bottom Line: The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model.The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation.This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, People's Republic of China.

ABSTRACT
Radiation pneumonitis (RP) is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomal curcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-κB pathway and downregulated inflammatory factors including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and transforming growth factor-β induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation. This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application.

Show MeSH
Related in: MedlinePlus