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A new strategy for TiO2 whiskers mediated multi-mode cancer treatment.

Xu P, Wang R, Ouyang J, Chen B - Nanoscale Res Lett (2015)

Bottom Line: Traditional Chinese medicine (TCM) which functions as chemotherapeutic or adjuvantly chemotherapeutic agents has been drawing a great many eyeballs for its easy obtain and significant antitumor effects accompanied with less toxic and side effects.These results identify TiO2 Ws of good biocompatibility and photocatalytic activity.These results reveal that such modality combinations put forward a promising proposal in cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008 People's Republic of China.

ABSTRACT
Traditional Chinese medicine (TCM) which functions as chemotherapeutic or adjuvantly chemotherapeutic agents has been drawing a great many eyeballs for its easy obtain and significant antitumor effects accompanied with less toxic and side effects. PDT (photodynamic therapy) utilizes the fact that certain compounds coined as photosensitizers, when exposed to light of a specific wavelength, are capable of generating cytotoxic reactive oxygen species (ROS) such as hydroxyl radical, hydrogen peroxide, and superoxide to kill cancer cells. Combinations of cancer therapeutic modalities are studied to improve the efficacy of treatment. This study aimed to explore a new strategy of coupling of titanium dioxide whiskers (TiO2 Ws) with the anticancer drug gambogic acid (GA) in photodynamic therapy. The nanocomposites were coined as GA-TiO2. The combination of TiO2 Ws with GA induced a remarkable enhancement in antitumor activity estimated by MTT assay, nuclear DAPI staining, and flow cytometry. Furthermore, the possible signaling pathway was explored by reverse transcription polymerase chain reaction (RT-PCR) and Western blot assay. These results identify TiO2 Ws of good biocompatibility and photocatalytic activity. In human leukemia cells (K562 cells), TiO2 Ws could obviously increase the intracellular concentration of GA and enhance its potential antitumor efficiency, suggesting that TiO2 Ws could act as an efficient drug delivery carrier targeting GA to carcinoma cells. Moreover, photodynamic GA-TiO2 nanocomposites could induce an evident reinforcement in antitumor activity with UV illumination. These results reveal that such modality combinations put forward a promising proposal in cancer therapy.

No MeSH data available.


Related in: MedlinePlus

Protein expression of apoptosis-associated genes by Western blot. K562 cells were treated with different reagents for 24 h. Notes: data were normalized to β-actin expression. (1) K562 cells were incubated with same volume of saline; (2) K562 cells were treated with GA; (3) K562 cells were incubated with GA-TiO2 nanocomposites; (4) K562 cells were incubated with GA-TiO2 nanocomposites with UV irradiation; data were figured as mean ± SD. #P < 0.05 when compared with the control group.
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Fig10: Protein expression of apoptosis-associated genes by Western blot. K562 cells were treated with different reagents for 24 h. Notes: data were normalized to β-actin expression. (1) K562 cells were incubated with same volume of saline; (2) K562 cells were treated with GA; (3) K562 cells were incubated with GA-TiO2 nanocomposites; (4) K562 cells were incubated with GA-TiO2 nanocomposites with UV irradiation; data were figured as mean ± SD. #P < 0.05 when compared with the control group.

Mentions: In cell proliferation, cyclin D1 displays the crucial function, which ensures the cell access to S period from G1 period. With the combination of cyclin D1 and CDK4, leading to the activation of CDK4, the activated CDK4 promotes the phosphorylation of the downstream pRb, in which way advances the cell cycle crossing over checkpoints and leads to abnormal proliferation. CDK2 combines with cyclin E as a complex and phosphorylates the downstream Rb, which induces the progression of cell cycle. P21 and P27 play an important role in inducing apoptosis of cells by competitively inhibiting the cyclin or cyclin-CDK, resulting in the loss of biological function of cyclin. PARP is the most important substrate of caspase-3, which is associated with DNA repair and monitoring of genetic integrity. PARP cannot develop its normal function when it is cut into two fragments by caspase-3, finally eliciting the apoptosis of cells. So we can see from Figure 9 that compared with the control group, transcription of CDK2, CDK4, and cyclin D1 messenger RNA (mRNA) was downregulated, and the expression levels of caspase-3, p21, and p27 were upregulated to some extent in GA, GA-TiO2 nanocomposites, and GA-TiO2 nanocomposites with UV irradiation. The same conclusion can be drawn from Figure 10. These results indicate that photodynamic TiO2 Ws could load GA to induce a marked improvement in antitumor activity in various apoptotic pathways.Figure 9


A new strategy for TiO2 whiskers mediated multi-mode cancer treatment.

Xu P, Wang R, Ouyang J, Chen B - Nanoscale Res Lett (2015)

Protein expression of apoptosis-associated genes by Western blot. K562 cells were treated with different reagents for 24 h. Notes: data were normalized to β-actin expression. (1) K562 cells were incubated with same volume of saline; (2) K562 cells were treated with GA; (3) K562 cells were incubated with GA-TiO2 nanocomposites; (4) K562 cells were incubated with GA-TiO2 nanocomposites with UV irradiation; data were figured as mean ± SD. #P < 0.05 when compared with the control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4385221&req=5

Fig10: Protein expression of apoptosis-associated genes by Western blot. K562 cells were treated with different reagents for 24 h. Notes: data were normalized to β-actin expression. (1) K562 cells were incubated with same volume of saline; (2) K562 cells were treated with GA; (3) K562 cells were incubated with GA-TiO2 nanocomposites; (4) K562 cells were incubated with GA-TiO2 nanocomposites with UV irradiation; data were figured as mean ± SD. #P < 0.05 when compared with the control group.
Mentions: In cell proliferation, cyclin D1 displays the crucial function, which ensures the cell access to S period from G1 period. With the combination of cyclin D1 and CDK4, leading to the activation of CDK4, the activated CDK4 promotes the phosphorylation of the downstream pRb, in which way advances the cell cycle crossing over checkpoints and leads to abnormal proliferation. CDK2 combines with cyclin E as a complex and phosphorylates the downstream Rb, which induces the progression of cell cycle. P21 and P27 play an important role in inducing apoptosis of cells by competitively inhibiting the cyclin or cyclin-CDK, resulting in the loss of biological function of cyclin. PARP is the most important substrate of caspase-3, which is associated with DNA repair and monitoring of genetic integrity. PARP cannot develop its normal function when it is cut into two fragments by caspase-3, finally eliciting the apoptosis of cells. So we can see from Figure 9 that compared with the control group, transcription of CDK2, CDK4, and cyclin D1 messenger RNA (mRNA) was downregulated, and the expression levels of caspase-3, p21, and p27 were upregulated to some extent in GA, GA-TiO2 nanocomposites, and GA-TiO2 nanocomposites with UV irradiation. The same conclusion can be drawn from Figure 10. These results indicate that photodynamic TiO2 Ws could load GA to induce a marked improvement in antitumor activity in various apoptotic pathways.Figure 9

Bottom Line: Traditional Chinese medicine (TCM) which functions as chemotherapeutic or adjuvantly chemotherapeutic agents has been drawing a great many eyeballs for its easy obtain and significant antitumor effects accompanied with less toxic and side effects.These results identify TiO2 Ws of good biocompatibility and photocatalytic activity.These results reveal that such modality combinations put forward a promising proposal in cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008 People's Republic of China.

ABSTRACT
Traditional Chinese medicine (TCM) which functions as chemotherapeutic or adjuvantly chemotherapeutic agents has been drawing a great many eyeballs for its easy obtain and significant antitumor effects accompanied with less toxic and side effects. PDT (photodynamic therapy) utilizes the fact that certain compounds coined as photosensitizers, when exposed to light of a specific wavelength, are capable of generating cytotoxic reactive oxygen species (ROS) such as hydroxyl radical, hydrogen peroxide, and superoxide to kill cancer cells. Combinations of cancer therapeutic modalities are studied to improve the efficacy of treatment. This study aimed to explore a new strategy of coupling of titanium dioxide whiskers (TiO2 Ws) with the anticancer drug gambogic acid (GA) in photodynamic therapy. The nanocomposites were coined as GA-TiO2. The combination of TiO2 Ws with GA induced a remarkable enhancement in antitumor activity estimated by MTT assay, nuclear DAPI staining, and flow cytometry. Furthermore, the possible signaling pathway was explored by reverse transcription polymerase chain reaction (RT-PCR) and Western blot assay. These results identify TiO2 Ws of good biocompatibility and photocatalytic activity. In human leukemia cells (K562 cells), TiO2 Ws could obviously increase the intracellular concentration of GA and enhance its potential antitumor efficiency, suggesting that TiO2 Ws could act as an efficient drug delivery carrier targeting GA to carcinoma cells. Moreover, photodynamic GA-TiO2 nanocomposites could induce an evident reinforcement in antitumor activity with UV illumination. These results reveal that such modality combinations put forward a promising proposal in cancer therapy.

No MeSH data available.


Related in: MedlinePlus