<abstract xmlns="http://www.w3.org/1999/xhtml">Increasing numbers of oncological patients and growing drug resistance ensure that new methods of cancer treatment are intensively sought. Combining drugs for a synergistic effect is one of several possible ways to mitigate this problem. This leads to reducing the effective drug dose and the occurrence of side effects. Doxorubicin (DOX) is an antineoplastic agent that has several mechanisms of action. DOX intercalates between base pairs of DNA helix, inhibits topoisomerase II and also forms reactive oxygen species. Bortezomib (BZT) is an antitumor agent belonging to the group of proteasome inhibitors. It has been observed that BZT triggers an oxidative stress response <italic>in vitro</italic> and <italic>in vivo</italic>.Accumulation of oxidatively damaged proteins and the simultaneously blocking of the proteasome can be very damaging to the tumour cell. For this reason, the aim of the study was to assess the potentially synergistic effect of DOX and BZT on human acute lymphoblastic leukemia (ALL). In the work, the cells were treated with both agents and their combinations and the effect was evaluated on the basis of morphological assessment, MTT assay and level of reduced glutathione measurement.The study has shown that on acute lymphoblastic leukemia cells, synergistic effects came about in the combination of 1nM BZT with a wide range of concentrations of DOX. Herein, the visible, coactive effect of DOX and BZT was observed on oxidative stress levels. This phenomenon can be essential in blunting the possibility of rapid manifestation of resistance seen in BZT monotherapy. In addition, the needed very low concentrations of DOX reduce the risk of therapy side effect.</abstract>

Increasing numbers of oncological patients and growing drug resistance ensure that new methods of cancer treatment are intensively sought. Combining drugs for a synergistic effect is one of several possible ways to mitigate this problem. This leads to reducing the effective drug dose and the occurrence of side effects. Doxorubicin (DOX) is an antineoplastic agent that has several mechanisms of action. DOX intercalates between base pairs of DNA helix, inhibits topoisomerase II and also forms reactive oxygen species. Bortezomib (BZT) is an antitumor agent belonging to the group of proteasome inhibitors. It has been observed that BZT triggers an oxidative stress response in vitro and in vivo.Accumulation of oxidatively damaged proteins and the simultaneously blocking of the proteasome can be very damaging to the tumour cell. For this reason, the aim of the study was to assess the potentially synergistic effect of DOX and BZT on human acute lymphoblastic leukemia (ALL). In the work, the cells were treated with both agents and their combinations and the effect was evaluated on the basis of morphological assessment, MTT assay and level of reduced glutathione measurement.The study has shown that on acute lymphoblastic leukemia cells, synergistic effects came about in the combination of 1nM BZT with a wide range of concentrations of DOX. Herein, the visible, coactive effect of DOX and BZT was observed on oxidative stress levels. This phenomenon can be essential in blunting the possibility of rapid manifestation of resistance seen in BZT monotherapy. In addition, the needed very low concentrations of DOX reduce the risk of therapy side effect.

Evaluation of the combined effects of doxorubicin and bortezomib on the human acute lymphoblastic leukemia cell line

Current Issues in Pharmacy and Medical Sciences

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Increasing numbers of oncological patients and growing drug resistance ensure that new methods of cancer treatment are intensively sought. Combining drugs for...

Evaluation of the combined effects of doxorubicin and bortezomib on the human acute lymphoblastic leukemia cell line

Published Online: Jul 02, 2019

Page range: 87 - 91

Received: Sep 21, 2018

Accepted: Nov 12, 2018

DOI: https://doi.org/10.2478/cipms-2019-0017

Keywords
doxorubicin, bortezomib, lymphoblastic leukemia, oxidative stress

© 2019 Agnieszka Korga et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Evaluation of the combined effects of doxorubicin and bortezomib on the human acute lymphoblastic leukemia cell line

Published Online: Jul 02, 2019

Page range: 87 - 91

Received: Sep 21, 2018

Accepted: Nov 12, 2018

DOI: https://doi.org/10.2478/cipms-2019-0017

Keywordsdoxorubicin, bortezomib, lymphoblastic leukemia, oxidative stress

© 2019 Agnieszka Korga et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Keywords
doxorubicin, bortezomib, lymphoblastic leukemia, oxidative stress