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Cisplatin in 5% Ethanol Eradicates Cisplatin-Resistant Lung Tumor by Killing Lung Cancer Side Population (SP) Cells and Non-SP Cells.

Niu Q, Wang W, Li Y, Ruden DM, Li Q, Wang F - Front Genet (2013)

Bottom Line: Furthermore, cytotoxic cisplatin (DDP) in 5% (vol/vol) ethanol kills SP plus non-SP cancer cells better than either treatment alone in eradicating chemoresistant lung tumors.We found that 5% ethanol did not reduce ABCG2 protein levels, but significantly reduced ABCG2 protein function by a Hoechst 33342 extrusion assay, an ATPase activity assay, and transmission electron microscopy.In DDP-resistant A549/DDP lung tumor-bearing Balb/C nude mice, intratumoral injection of 5% ethanol-DDP regressed tumors and significantly improved survivals compared with 5% ethanol, DDP alone, or control.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, No. 309 People's Liberation Army Hospital Beijing, People's Republic of China.

ABSTRACT
Cancer side population (SP) cells with cancer stem cell-like properties are thought to be responsible for lung cancer chemotherapy resistance and currently no drug can efficiently target them. Breast cancer resistance protein (BRCP/ABCG2) is a major drug transporter in protecting lung cancer SP cells from cytotoxic agents. We showed that a low concentration of ethanol, which inhibits many membrane proteins, inhibits ABCG2 in lung cancer SP cells. Furthermore, cytotoxic cisplatin (DDP) in 5% (vol/vol) ethanol kills SP plus non-SP cancer cells better than either treatment alone in eradicating chemoresistant lung tumors. We found that 5% ethanol did not reduce ABCG2 protein levels, but significantly reduced ABCG2 protein function by a Hoechst 33342 extrusion assay, an ATPase activity assay, and transmission electron microscopy. Further, DDP in 5% ethanol (5% ethanol-DDP) induced apoptosis of the SP plus non-SP cancer cells both in vitro and in vivo. In DDP-resistant A549/DDP lung tumor-bearing Balb/C nude mice, intratumoral injection of 5% ethanol-DDP regressed tumors and significantly improved survivals compared with 5% ethanol, DDP alone, or control. Intratumoral injection of 5% ethanol-DDP helped eradicate tumors in 30% (3/10) of the mice after 4 weeks treatment. By killing SP and non-SP cancer cells, 5% ethanol-DDP could eradicate DDP-resistant lung tumor and extend survival, providing a novel way to improve chemoresistant lung cancer survival for clinic.

No MeSH data available.


Related in: MedlinePlus

(A) Apoptosis analysis of 5% ethanol–DDP-treated tumor tissues with TUNEL staining. (a) Control tumor tissue. (b) 5% ethanol–DDP treated tumor tissue. Compared with control, 5% ethanol–DDP significantlyIn artworks of Figure 3 has no part whereas the parts (A) and (B) explained in the caption. Kindly advise. increased tumor cell apoptosis rate (60.11% ± 7.52% vs. 5.32% ± 1.76%, p < 0.05). (B) DDP-resistant tumor size changes by various treatments.5% ethanol–DDP significantly inhibited tumor growth compared with control or DDP alone or 5% ethanol after 4 weeks’ treatment. E–D stands for ethanol–cisplatin. (C) Survival of A549/DDP tumor-bearing mice in different groups. 5% ethanol–DDP treatment significantly improved estimated mean survival time compared with control or DDP alone or 5% ethanol. E–D stands for ethanol–cisplatin.
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Figure 3: (A) Apoptosis analysis of 5% ethanol–DDP-treated tumor tissues with TUNEL staining. (a) Control tumor tissue. (b) 5% ethanol–DDP treated tumor tissue. Compared with control, 5% ethanol–DDP significantlyIn artworks of Figure 3 has no part whereas the parts (A) and (B) explained in the caption. Kindly advise. increased tumor cell apoptosis rate (60.11% ± 7.52% vs. 5.32% ± 1.76%, p < 0.05). (B) DDP-resistant tumor size changes by various treatments.5% ethanol–DDP significantly inhibited tumor growth compared with control or DDP alone or 5% ethanol after 4 weeks’ treatment. E–D stands for ethanol–cisplatin. (C) Survival of A549/DDP tumor-bearing mice in different groups. 5% ethanol–DDP treatment significantly improved estimated mean survival time compared with control or DDP alone or 5% ethanol. E–D stands for ethanol–cisplatin.

Mentions: Compared with control, 5% ethanol–DDP increased apoptotic cells as shown in Figure 3A. The rates of total apoptotic cells were 60.11% ± 7.52% in the 5% ethanol–DDP-treated tumor tissues and 5.32% ± 1.76% in the control tumor tissues. 5% ethanol–DDP caused an 11.3-fold increase of apoptosis (Figure 3A).


Cisplatin in 5% Ethanol Eradicates Cisplatin-Resistant Lung Tumor by Killing Lung Cancer Side Population (SP) Cells and Non-SP Cells.

Niu Q, Wang W, Li Y, Ruden DM, Li Q, Wang F - Front Genet (2013)

(A) Apoptosis analysis of 5% ethanol–DDP-treated tumor tissues with TUNEL staining. (a) Control tumor tissue. (b) 5% ethanol–DDP treated tumor tissue. Compared with control, 5% ethanol–DDP significantlyIn artworks of Figure 3 has no part whereas the parts (A) and (B) explained in the caption. Kindly advise. increased tumor cell apoptosis rate (60.11% ± 7.52% vs. 5.32% ± 1.76%, p < 0.05). (B) DDP-resistant tumor size changes by various treatments.5% ethanol–DDP significantly inhibited tumor growth compared with control or DDP alone or 5% ethanol after 4 weeks’ treatment. E–D stands for ethanol–cisplatin. (C) Survival of A549/DDP tumor-bearing mice in different groups. 5% ethanol–DDP treatment significantly improved estimated mean survival time compared with control or DDP alone or 5% ethanol. E–D stands for ethanol–cisplatin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756282&req=5

Figure 3: (A) Apoptosis analysis of 5% ethanol–DDP-treated tumor tissues with TUNEL staining. (a) Control tumor tissue. (b) 5% ethanol–DDP treated tumor tissue. Compared with control, 5% ethanol–DDP significantlyIn artworks of Figure 3 has no part whereas the parts (A) and (B) explained in the caption. Kindly advise. increased tumor cell apoptosis rate (60.11% ± 7.52% vs. 5.32% ± 1.76%, p < 0.05). (B) DDP-resistant tumor size changes by various treatments.5% ethanol–DDP significantly inhibited tumor growth compared with control or DDP alone or 5% ethanol after 4 weeks’ treatment. E–D stands for ethanol–cisplatin. (C) Survival of A549/DDP tumor-bearing mice in different groups. 5% ethanol–DDP treatment significantly improved estimated mean survival time compared with control or DDP alone or 5% ethanol. E–D stands for ethanol–cisplatin.
Mentions: Compared with control, 5% ethanol–DDP increased apoptotic cells as shown in Figure 3A. The rates of total apoptotic cells were 60.11% ± 7.52% in the 5% ethanol–DDP-treated tumor tissues and 5.32% ± 1.76% in the control tumor tissues. 5% ethanol–DDP caused an 11.3-fold increase of apoptosis (Figure 3A).

Bottom Line: Furthermore, cytotoxic cisplatin (DDP) in 5% (vol/vol) ethanol kills SP plus non-SP cancer cells better than either treatment alone in eradicating chemoresistant lung tumors.We found that 5% ethanol did not reduce ABCG2 protein levels, but significantly reduced ABCG2 protein function by a Hoechst 33342 extrusion assay, an ATPase activity assay, and transmission electron microscopy.In DDP-resistant A549/DDP lung tumor-bearing Balb/C nude mice, intratumoral injection of 5% ethanol-DDP regressed tumors and significantly improved survivals compared with 5% ethanol, DDP alone, or control.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, No. 309 People's Liberation Army Hospital Beijing, People's Republic of China.

ABSTRACT
Cancer side population (SP) cells with cancer stem cell-like properties are thought to be responsible for lung cancer chemotherapy resistance and currently no drug can efficiently target them. Breast cancer resistance protein (BRCP/ABCG2) is a major drug transporter in protecting lung cancer SP cells from cytotoxic agents. We showed that a low concentration of ethanol, which inhibits many membrane proteins, inhibits ABCG2 in lung cancer SP cells. Furthermore, cytotoxic cisplatin (DDP) in 5% (vol/vol) ethanol kills SP plus non-SP cancer cells better than either treatment alone in eradicating chemoresistant lung tumors. We found that 5% ethanol did not reduce ABCG2 protein levels, but significantly reduced ABCG2 protein function by a Hoechst 33342 extrusion assay, an ATPase activity assay, and transmission electron microscopy. Further, DDP in 5% ethanol (5% ethanol-DDP) induced apoptosis of the SP plus non-SP cancer cells both in vitro and in vivo. In DDP-resistant A549/DDP lung tumor-bearing Balb/C nude mice, intratumoral injection of 5% ethanol-DDP regressed tumors and significantly improved survivals compared with 5% ethanol, DDP alone, or control. Intratumoral injection of 5% ethanol-DDP helped eradicate tumors in 30% (3/10) of the mice after 4 weeks treatment. By killing SP and non-SP cancer cells, 5% ethanol-DDP could eradicate DDP-resistant lung tumor and extend survival, providing a novel way to improve chemoresistant lung cancer survival for clinic.

No MeSH data available.


Related in: MedlinePlus