Skip to content
Back to outputs

Pharmacological development of target-specific delocalized lipophilic cation-functionalized carboranes for cancer therapy

Research output: Contribution to journalArticle

Standard

Pharmacological development of target-specific delocalized lipophilic cation-functionalized carboranes for cancer therapy. / Tseligka, Eirini D.; Rova, Aikaterini; Amanatiadou, Elsa P.; Calabrese, Gianpiero; Tsibouklis, John; Fatouros, Dimitrios G.; Vizirianakis, Ioannis S.

In: Pharmaceutical Research, Vol. 33, No. 8, 08.2016, p. 1945-1958.

Research output: Contribution to journalArticle

Harvard

Tseligka, ED, Rova, A, Amanatiadou, EP, Calabrese, G, Tsibouklis, J, Fatouros, DG & Vizirianakis, IS 2016, 'Pharmacological development of target-specific delocalized lipophilic cation-functionalized carboranes for cancer therapy', Pharmaceutical Research, vol. 33, no. 8, pp. 1945-1958. https://doi.org/10.1007/s11095-016-1930-4

APA

Tseligka, E. D., Rova, A., Amanatiadou, E. P., Calabrese, G., Tsibouklis, J., Fatouros, D. G., & Vizirianakis, I. S. (2016). Pharmacological development of target-specific delocalized lipophilic cation-functionalized carboranes for cancer therapy. Pharmaceutical Research, 33(8), 1945-1958. https://doi.org/10.1007/s11095-016-1930-4

Vancouver

Tseligka ED, Rova A, Amanatiadou EP, Calabrese G, Tsibouklis J, Fatouros DG et al. Pharmacological development of target-specific delocalized lipophilic cation-functionalized carboranes for cancer therapy. Pharmaceutical Research. 2016 Aug;33(8):1945-1958. https://doi.org/10.1007/s11095-016-1930-4

Author

Tseligka, Eirini D. ; Rova, Aikaterini ; Amanatiadou, Elsa P. ; Calabrese, Gianpiero ; Tsibouklis, John ; Fatouros, Dimitrios G. ; Vizirianakis, Ioannis S. / Pharmacological development of target-specific delocalized lipophilic cation-functionalized carboranes for cancer therapy. In: Pharmaceutical Research. 2016 ; Vol. 33, No. 8. pp. 1945-1958.

Bibtex

@article{b8052ebc24c447d48cbf48b2f3237d59,
title = "Pharmacological development of target-specific delocalized lipophilic cation-functionalized carboranes for cancer therapy",
abstract = "Purpose Tumor cell heterogeneity and microenvironment represent major hindering factors in the clinical setting toward achieving the desired selectivity and specificity to malignant tissues for molecularly targeted cancer therapeutics. In this study, the cellular and molecular evaluation of several delocalized lipophilic cation (DLC)-functionalized carborane compounds as innovative anticancer agents is presented. Methods The anticancer potential assessment of the DLC-carboranes was performed in established normal (MRC-5, Vero), cancer (U-87 MG, HSC-3) and primary glioblastoma cancer stem (EGFRpos, EGFRneg) cultures. Moreover, the molecular mechanism of action underlying their pharmacological response is also analyzed. Results The pharmacological anticancer profile of DLC-functionalized carboranes is characterized by: a) a marked in vitro selectivity, due to lower concentration range needed (ca. 10 fold) to exert their cell growth-arrest effect on U-87 MG and HSC-3, as compared with that on MRC-5 and Vero; b) a similar selective growth inhibition behavior towards EGFRpos and EGFRneg cultures (>10 fold difference in potency) without, however, the activation of apoptosis in cultures; c) notably, in marked contrast to cancer cells, normal cells are capable of recapitulating their full proliferation potential following exposure to DLC-carboranes; and, d) such pharmacological effects of DLC-carboranes has been unveiled to be elicited at the molecular level through activation of the p53/p21 axis. Conclusions Overall, the data presented in this work indicates the potential of the DLC-functionalized carboranes to act as new selective anticancer therapeutics that may be used autonomously or in therapies involving radiation with thermal neutrons. Importantly, such bifunctional capacity may be beneficial in cancer therapy.",
author = "Tseligka, {Eirini D.} and Aikaterini Rova and Amanatiadou, {Elsa P.} and Gianpiero Calabrese and John Tsibouklis and Fatouros, {Dimitrios G.} and Vizirianakis, {Ioannis S.}",
year = "2016",
month = "8",
doi = "10.1007/s11095-016-1930-4",
language = "English",
volume = "33",
pages = "1945--1958",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "8",

}

RIS

TY - JOUR

T1 - Pharmacological development of target-specific delocalized lipophilic cation-functionalized carboranes for cancer therapy

AU - Tseligka, Eirini D.

AU - Rova, Aikaterini

AU - Amanatiadou, Elsa P.

AU - Calabrese, Gianpiero

AU - Tsibouklis, John

AU - Fatouros, Dimitrios G.

AU - Vizirianakis, Ioannis S.

PY - 2016/8

Y1 - 2016/8

N2 - Purpose Tumor cell heterogeneity and microenvironment represent major hindering factors in the clinical setting toward achieving the desired selectivity and specificity to malignant tissues for molecularly targeted cancer therapeutics. In this study, the cellular and molecular evaluation of several delocalized lipophilic cation (DLC)-functionalized carborane compounds as innovative anticancer agents is presented. Methods The anticancer potential assessment of the DLC-carboranes was performed in established normal (MRC-5, Vero), cancer (U-87 MG, HSC-3) and primary glioblastoma cancer stem (EGFRpos, EGFRneg) cultures. Moreover, the molecular mechanism of action underlying their pharmacological response is also analyzed. Results The pharmacological anticancer profile of DLC-functionalized carboranes is characterized by: a) a marked in vitro selectivity, due to lower concentration range needed (ca. 10 fold) to exert their cell growth-arrest effect on U-87 MG and HSC-3, as compared with that on MRC-5 and Vero; b) a similar selective growth inhibition behavior towards EGFRpos and EGFRneg cultures (>10 fold difference in potency) without, however, the activation of apoptosis in cultures; c) notably, in marked contrast to cancer cells, normal cells are capable of recapitulating their full proliferation potential following exposure to DLC-carboranes; and, d) such pharmacological effects of DLC-carboranes has been unveiled to be elicited at the molecular level through activation of the p53/p21 axis. Conclusions Overall, the data presented in this work indicates the potential of the DLC-functionalized carboranes to act as new selective anticancer therapeutics that may be used autonomously or in therapies involving radiation with thermal neutrons. Importantly, such bifunctional capacity may be beneficial in cancer therapy.

AB - Purpose Tumor cell heterogeneity and microenvironment represent major hindering factors in the clinical setting toward achieving the desired selectivity and specificity to malignant tissues for molecularly targeted cancer therapeutics. In this study, the cellular and molecular evaluation of several delocalized lipophilic cation (DLC)-functionalized carborane compounds as innovative anticancer agents is presented. Methods The anticancer potential assessment of the DLC-carboranes was performed in established normal (MRC-5, Vero), cancer (U-87 MG, HSC-3) and primary glioblastoma cancer stem (EGFRpos, EGFRneg) cultures. Moreover, the molecular mechanism of action underlying their pharmacological response is also analyzed. Results The pharmacological anticancer profile of DLC-functionalized carboranes is characterized by: a) a marked in vitro selectivity, due to lower concentration range needed (ca. 10 fold) to exert their cell growth-arrest effect on U-87 MG and HSC-3, as compared with that on MRC-5 and Vero; b) a similar selective growth inhibition behavior towards EGFRpos and EGFRneg cultures (>10 fold difference in potency) without, however, the activation of apoptosis in cultures; c) notably, in marked contrast to cancer cells, normal cells are capable of recapitulating their full proliferation potential following exposure to DLC-carboranes; and, d) such pharmacological effects of DLC-carboranes has been unveiled to be elicited at the molecular level through activation of the p53/p21 axis. Conclusions Overall, the data presented in this work indicates the potential of the DLC-functionalized carboranes to act as new selective anticancer therapeutics that may be used autonomously or in therapies involving radiation with thermal neutrons. Importantly, such bifunctional capacity may be beneficial in cancer therapy.

U2 - 10.1007/s11095-016-1930-4

DO - 10.1007/s11095-016-1930-4

M3 - Article

VL - 33

SP - 1945

EP - 1958

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 8

ER -

ID: 3957931