TY - JOUR
T1 - Microfocus x-ray fluorescence mapping of tumour penetration by an organo‑osmium anticancer complex
AU - Sanchez-Cano, Carlos
AU - Romero-Canelón, Isolda
AU - Geraki, Kalotina
AU - Sadler, Peter J
N1 - Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2018/8
Y1 - 2018/8
N2 - Microfocus synchrotron x-ray fluorescence (SXRF) imaging focussed on detection of the Os LIII edge shows that the organo‑osmium metallodrug candidate [(ŋ6-p-cym)Os(Azpy-NMe2)I]+ (p-cym = p-cymene, Azpy-NMe2 = 2-(p-([dimethylamino]phenylazo)pyridine)) [1] penetrates efficiently into the interior of A2780 human ovarian cancer cell spheroids, a model for a solid tumour. The accompanying changes in Zn and Ca distribution suggest that the complex causes nuclear damage and initiates signalling events for cell death, consistent with findings for cultured cancer cell monolayers. Such tumour penetration is likely to be important for combatting resistance to chemotherapy, which is becoming a problem for current clinical platinum drugs.
AB - Microfocus synchrotron x-ray fluorescence (SXRF) imaging focussed on detection of the Os LIII edge shows that the organo‑osmium metallodrug candidate [(ŋ6-p-cym)Os(Azpy-NMe2)I]+ (p-cym = p-cymene, Azpy-NMe2 = 2-(p-([dimethylamino]phenylazo)pyridine)) [1] penetrates efficiently into the interior of A2780 human ovarian cancer cell spheroids, a model for a solid tumour. The accompanying changes in Zn and Ca distribution suggest that the complex causes nuclear damage and initiates signalling events for cell death, consistent with findings for cultured cancer cell monolayers. Such tumour penetration is likely to be important for combatting resistance to chemotherapy, which is becoming a problem for current clinical platinum drugs.
KW - Organometallic metallodrugs
KW - 3D spheroids
KW - Tumour penetration
KW - Elemental mapping
KW - X-ray fluorescence
U2 - 10.1016/j.jinorgbio.2018.04.014
DO - 10.1016/j.jinorgbio.2018.04.014
M3 - Article
C2 - 29730234
SN - 0162-0134
VL - 185
SP - 26
EP - 29
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
ER -