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Trans,trans,trans-[PtIV(N3)2(OH)2(py)(NH3)]

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Trans,trans,trans-[PtIV(N3)2(OH)2(py)(NH3)] : A Light-Activated Antitumor Platinum Complex That Kills Human Cancer Cells by an Apoptosis-Independent Mechanism. / Westendorf, Aron F.; Woods, Julie A.; Korpis, Katharina; Farrer, Nicola J.; Salassa, Luca; Robinson, Kim; Appleyard, Virginia; Murray, Karen; Grünert, Renate; Thompson, Alastair M.; Sadler, Peter J.; Bednarski, Patrick J.

In: Molecular Cancer Therapeutics, Vol. 11, No. 9, 2012, p. 1894-1904.

Research output: Contribution to journalArticle

Harvard

Westendorf, AF, Woods, JA, Korpis, K, Farrer, NJ, Salassa, L, Robinson, K, Appleyard, V, Murray, K, Grünert, R, Thompson, AM, Sadler, PJ & Bednarski, PJ 2012, 'Trans,trans,trans-[PtIV(N3)2(OH)2(py)(NH3)]: A Light-Activated Antitumor Platinum Complex That Kills Human Cancer Cells by an Apoptosis-Independent Mechanism' Molecular Cancer Therapeutics, vol 11, no. 9, pp. 1894-1904.

APA

Westendorf, A. F., Woods, J. A., Korpis, K., Farrer, N. J., Salassa, L., Robinson, K., Appleyard, V., Murray, K., Grünert, R., Thompson, A. M., Sadler, P. J., & Bednarski, P. J. (2012). Trans,trans,trans-[PtIV(N3)2(OH)2(py)(NH3)]: A Light-Activated Antitumor Platinum Complex That Kills Human Cancer Cells by an Apoptosis-Independent Mechanism. Molecular Cancer Therapeutics, 11(9), 1894-1904doi: 10.1158/1535-7163.MCT-11-0959

Vancouver

Westendorf AF, Woods JA, Korpis K, Farrer NJ, Salassa L, Robinson K et al. Trans,trans,trans-[PtIV(N3)2(OH)2(py)(NH3)]: A Light-Activated Antitumor Platinum Complex That Kills Human Cancer Cells by an Apoptosis-Independent Mechanism. Molecular Cancer Therapeutics. 2012;11(9):1894-1904.

Author

Westendorf, Aron F.; Woods, Julie A.; Korpis, Katharina; Farrer, Nicola J.; Salassa, Luca; Robinson, Kim; Appleyard, Virginia; Murray, Karen; Grünert, Renate; Thompson, Alastair M.; Sadler, Peter J.; Bednarski, Patrick J. / Trans,trans,trans-[PtIV(N3)2(OH)2(py)(NH3)] : A Light-Activated Antitumor Platinum Complex That Kills Human Cancer Cells by an Apoptosis-Independent Mechanism.

In: Molecular Cancer Therapeutics, Vol. 11, No. 9, 2012, p. 1894-1904.

Research output: Contribution to journalArticle

Bibtex - Download

@article{f1f34ef98b954fb88230b508175e40dd,
title = "Trans,trans,trans-[PtIV(N3)2(OH)2(py)(NH3)]",
author = "Westendorf, {Aron F.} and Woods, {Julie A.} and Katharina Korpis and Farrer, {Nicola J.} and Luca Salassa and Kim Robinson and Virginia Appleyard and Karen Murray and Renate Grünert and Thompson, {Alastair M.} and Sadler, {Peter J.} and Bednarski, {Patrick J.}",
year = "2012",
volume = "11",
number = "9",
pages = "1894--1904",
journal = "Molecular Cancer Therapeutics",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Trans,trans,trans-[PtIV(N3)2(OH)2(py)(NH3)]

T2 - A Light-Activated Antitumor Platinum Complex That Kills Human Cancer Cells by an Apoptosis-Independent Mechanism

A1 - Westendorf,Aron F.

A1 - Woods,Julie A.

A1 - Korpis,Katharina

A1 - Farrer,Nicola J.

A1 - Salassa,Luca

A1 - Robinson,Kim

A1 - Appleyard,Virginia

A1 - Murray,Karen

A1 - Grünert,Renate

A1 - Thompson,Alastair M.

A1 - Sadler,Peter J.

A1 - Bednarski,Patrick J.

AU - Westendorf,Aron F.

AU - Woods,Julie A.

AU - Korpis,Katharina

AU - Farrer,Nicola J.

AU - Salassa,Luca

AU - Robinson,Kim

AU - Appleyard,Virginia

AU - Murray,Karen

AU - Grünert,Renate

AU - Thompson,Alastair M.

AU - Sadler,Peter J.

AU - Bednarski,Patrick J.

PY - 2012

Y1 - 2012

N2 - Photoactivatable Pt(IV) diazido complexes have unusual photobiologic properties. We show here that trans,trans,trans-[Pt(IV)(N(3))(2)(OH)(2)(py)(NH(3))] complex 3 is a potent photoactivated cytotoxin toward human cancer cells in culture, with an average IC(50) value in 13 cell lines of 55 ± 28 µmol/L after 30 minutes (0.12 mW/cm(2)) photoactivation with UVA, although visible light was also effective. Photoactivated complex 3 was noncross-resistant to cisplatin in 3 of 4 resistant cell lines. Cell swelling but very little blebbing was seen for HL60 cells treated with irradiated complex 3. Unlike cisplatin and etoposide, both of which cause apoptosis in HL60 cells, no apoptosis was observed for UVA-activated complex 3 by the Annexin V/propidium iodide flow cytotometry assay. Changes in the levels of the autophagic proteins LC3B-II and p62 in HL60 cells treated with UVA-activated complex 3 indicate autophagy is active during cell death. In a clonogenic assay with the SISO human cervix cancer cell line, 3 inhibited colony formation when activated by UVA irradiation. Antitumor activity of complex 3 in mice bearing xenografted OE19 esophageal carcinoma tumors was photoaugmented by visible light. Insights into the novel reaction pathways of complex 3 have been obtained from (14)N{(1)H} nuclear magnetic resonance studies, which show that photoactivation pathways can involve release of free azide in buffered solution. Density functional theory (DFT) and time-dependent DFT calculations revealed the dissociative character of singlet and triplet excited states of complex 3, which gives rise to reactive, possibly cytotoxic azidyl radicals. Mol Cancer Ther; 11(9); 1894-904. ©2012 AACR.

AB - Photoactivatable Pt(IV) diazido complexes have unusual photobiologic properties. We show here that trans,trans,trans-[Pt(IV)(N(3))(2)(OH)(2)(py)(NH(3))] complex 3 is a potent photoactivated cytotoxin toward human cancer cells in culture, with an average IC(50) value in 13 cell lines of 55 ± 28 µmol/L after 30 minutes (0.12 mW/cm(2)) photoactivation with UVA, although visible light was also effective. Photoactivated complex 3 was noncross-resistant to cisplatin in 3 of 4 resistant cell lines. Cell swelling but very little blebbing was seen for HL60 cells treated with irradiated complex 3. Unlike cisplatin and etoposide, both of which cause apoptosis in HL60 cells, no apoptosis was observed for UVA-activated complex 3 by the Annexin V/propidium iodide flow cytotometry assay. Changes in the levels of the autophagic proteins LC3B-II and p62 in HL60 cells treated with UVA-activated complex 3 indicate autophagy is active during cell death. In a clonogenic assay with the SISO human cervix cancer cell line, 3 inhibited colony formation when activated by UVA irradiation. Antitumor activity of complex 3 in mice bearing xenografted OE19 esophageal carcinoma tumors was photoaugmented by visible light. Insights into the novel reaction pathways of complex 3 have been obtained from (14)N{(1)H} nuclear magnetic resonance studies, which show that photoactivation pathways can involve release of free azide in buffered solution. Density functional theory (DFT) and time-dependent DFT calculations revealed the dissociative character of singlet and triplet excited states of complex 3, which gives rise to reactive, possibly cytotoxic azidyl radicals. Mol Cancer Ther; 11(9); 1894-904. ©2012 AACR.

U2 - 10.1158/1535-7163.MCT-11-0959

DO - 10.1158/1535-7163.MCT-11-0959

M1 - Article

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

IS - 9

VL - 11

SP - 1894

EP - 1904

ER -

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