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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 inhibits the activation of macrophages and downregulates the serum levels of pro-inflammatory cytokines. The inhibitory effect of Curcumin on activation of macrophages was detected first. (A) Curcumin inhibited the activity of NF-κB of macrophages. (B) Curcumin blocked the migration of macrophages (MCP-1, Cur: Cur+MCP-1, AS605240: AS605240+MCP-1). Then, the serum levels of both the Lipo and Lipo-cur group for IL-6, IL-8, TNF-α, and TGF-β cytokine concentration were measured at the first month of RP, mice in each group were bled for serum at the end of week 1, 2, 3, and 4 after being treated with Lipo or Lipo-cur. (C) The level of TGF-β from the Lipo-cur treatment group and the Lipo group. (D) The level of TNF-α from the Lipo-cur treatment group and the Lipo group. (E) The level of IL-8 from the Lipo-cur treatment group and the Lipo group. (F) The level of IL-6 from the Lipo-cur treatment group and the Lipo group.Notes: Data are mean ± standard error of the mean; *denotes P < 0.05 between groups.Abbreviations: Cur, curcumin; IL, interleukin; Lipo, empty liposome; Lipo-cur, liposomal curcumin; MCP, monocyte chemotactic protein; NF, nuclear factor; TGF, transforming growth factor; TNF, tumor necrosis factor.
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f5-ijn-7-2601: Lipo-cur inhibits the activation of macrophages and downregulates the serum levels of pro-inflammatory cytokines. The inhibitory effect of Curcumin on activation of macrophages was detected first. (A) Curcumin inhibited the activity of NF-κB of macrophages. (B) Curcumin blocked the migration of macrophages (MCP-1, Cur: Cur+MCP-1, AS605240: AS605240+MCP-1). Then, the serum levels of both the Lipo and Lipo-cur group for IL-6, IL-8, TNF-α, and TGF-β cytokine concentration were measured at the first month of RP, mice in each group were bled for serum at the end of week 1, 2, 3, and 4 after being treated with Lipo or Lipo-cur. (C) The level of TGF-β from the Lipo-cur treatment group and the Lipo group. (D) The level of TNF-α from the Lipo-cur treatment group and the Lipo group. (E) The level of IL-8 from the Lipo-cur treatment group and the Lipo group. (F) The level of IL-6 from the Lipo-cur treatment group and the Lipo group.Notes: Data are mean ± standard error of the mean; *denotes P < 0.05 between groups.Abbreviations: Cur, curcumin; IL, interleukin; Lipo, empty liposome; Lipo-cur, liposomal curcumin; MCP, monocyte chemotactic protein; NF, nuclear factor; TGF, transforming growth factor; TNF, tumor necrosis factor.

Mentions: As a result of clearing apoptotic cells or as a direct response to radiation, the activation of macrophages may cause cytokine production, leading to lung injury.33 Here, the inhibitory effects of curcumin on activation of macrophages was investigated. The results showed that curcumin not only inhibited the activity of NF-κB, but also blocked the migration of macrophages (Figure 5A and B). In vivo, plasma levels of both curcumin and NS group for IL-6, IL-8, TNF-α, and TGF-β cytokine concentration were measured at the first month of RP. The level of TGF-β from the Lipo-cur treatment group was lower than the NS group from the first week to the fourth week. Moreover, the level of TGF-β in the third week and fourth week was lower than that in the first week and second week in the Lipo-cur treatment group (Figure 5C). No difference of TNF-α and IL-8 was observed between the NS group and Lipo-cur group after the first week, but the level of TNF-α and IL-8 of the Lipo-cur group was lower than in the NS group after the second week (Figure 5D and E). The level of IL-6 from the Lipo-cur treatment group was lower than the NS group from the first week to the fourth week; it reached its peak at the second week and then showed a gradual downward trend (Figure 5F).


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 inhibits the activation of macrophages and downregulates the serum levels of pro-inflammatory cytokines. The inhibitory effect of Curcumin on activation of macrophages was detected first. (A) Curcumin inhibited the activity of NF-κB of macrophages. (B) Curcumin blocked the migration of macrophages (MCP-1, Cur: Cur+MCP-1, AS605240: AS605240+MCP-1). Then, the serum levels of both the Lipo and Lipo-cur group for IL-6, IL-8, TNF-α, and TGF-β cytokine concentration were measured at the first month of RP, mice in each group were bled for serum at the end of week 1, 2, 3, and 4 after being treated with Lipo or Lipo-cur. (C) The level of TGF-β from the Lipo-cur treatment group and the Lipo group. (D) The level of TNF-α from the Lipo-cur treatment group and the Lipo group. (E) The level of IL-8 from the Lipo-cur treatment group and the Lipo group. (F) The level of IL-6 from the Lipo-cur treatment group and the Lipo group.Notes: Data are mean ± standard error of the mean; *denotes P < 0.05 between groups.Abbreviations: Cur, curcumin; IL, interleukin; Lipo, empty liposome; Lipo-cur, liposomal curcumin; MCP, monocyte chemotactic protein; NF, nuclear factor; TGF, transforming growth factor; TNF, tumor necrosis factor.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368513&req=5

f5-ijn-7-2601: Lipo-cur inhibits the activation of macrophages and downregulates the serum levels of pro-inflammatory cytokines. The inhibitory effect of Curcumin on activation of macrophages was detected first. (A) Curcumin inhibited the activity of NF-κB of macrophages. (B) Curcumin blocked the migration of macrophages (MCP-1, Cur: Cur+MCP-1, AS605240: AS605240+MCP-1). Then, the serum levels of both the Lipo and Lipo-cur group for IL-6, IL-8, TNF-α, and TGF-β cytokine concentration were measured at the first month of RP, mice in each group were bled for serum at the end of week 1, 2, 3, and 4 after being treated with Lipo or Lipo-cur. (C) The level of TGF-β from the Lipo-cur treatment group and the Lipo group. (D) The level of TNF-α from the Lipo-cur treatment group and the Lipo group. (E) The level of IL-8 from the Lipo-cur treatment group and the Lipo group. (F) The level of IL-6 from the Lipo-cur treatment group and the Lipo group.Notes: Data are mean ± standard error of the mean; *denotes P < 0.05 between groups.Abbreviations: Cur, curcumin; IL, interleukin; Lipo, empty liposome; Lipo-cur, liposomal curcumin; MCP, monocyte chemotactic protein; NF, nuclear factor; TGF, transforming growth factor; TNF, tumor necrosis factor.
Mentions: As a result of clearing apoptotic cells or as a direct response to radiation, the activation of macrophages may cause cytokine production, leading to lung injury.33 Here, the inhibitory effects of curcumin on activation of macrophages was investigated. The results showed that curcumin not only inhibited the activity of NF-κB, but also blocked the migration of macrophages (Figure 5A and B). In vivo, plasma levels of both curcumin and NS group for IL-6, IL-8, TNF-α, and TGF-β cytokine concentration were measured at the first month of RP. The level of TGF-β from the Lipo-cur treatment group was lower than the NS group from the first week to the fourth week. Moreover, the level of TGF-β in the third week and fourth week was lower than that in the first week and second week in the Lipo-cur treatment group (Figure 5C). No difference of TNF-α and IL-8 was observed between the NS group and Lipo-cur group after the first week, but the level of TNF-α and IL-8 of the Lipo-cur group was lower than in the NS group after the second week (Figure 5D and E). The level of IL-6 from the Lipo-cur treatment group was lower than the NS group from the first week to the fourth week; it reached its peak at the second week and then showed a gradual downward trend (Figure 5F).

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