PhD Scientific Days 2020

Alpha-Lipoic Acid Alters the Antitumor Effect of Bortezomib in Melanoma Cells In Vitro

Előadó neve

Takács, Angéla

Előadó munkahelye

Department of Genetics, Cell- and Immunobiology

Előadó telefonszáma

36302379584

Előadó e-mail címe

angela.takacs1@gmail.com

Az előadás címe

Alpha-Lipoic Acid Alters the Antitumor Effect of Bortezomib in Melanoma Cells In Vitro

Szerző(k) neve és munkahelye

Takács, A.1; Lajkó, E.1; Láng, O.1; Istenes, I.1; Kőhidai, L.1

1 Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary
2 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary

Language of the presentation

Hungarian

Section, first choice

Pharmaceutical Sciences

Section, second choice

Pathology and Oncology

Összefoglaló szövege

Background: Bortezomib (BOZ) is a proteasome inhibitor chemotherapeutic agent utilized to treat multiple myeloma and recently offered to cure melanoma. Bortezomib-induced peripheral neuropathy is one of the most significant and dose-limiting side-effects, which can be treated with antioxidants (e.g. alpha-lipoic acid - ALA and vitamin B1 - vit B1) as a part of cancer supportive care. We hypothesized that these antioxidants may counteract the antitumor activity of BOZ.
Aims: The objectives of our experiments were: (i) to verify the cytotoxicity of BOZ; (ii) to test and compare the influence of the antioxidants on the antitumor effect of BOZ in melanoma (A2058) and myeloma (U266) cells as clinically relevant target cells.
Methods: The cell viability was determined by xCELLigence® RTCA SP instrument and by a cell based CellTiter-Glo® Luminescent Cell Viability Assay. Then the possible molecular pattern was characterized by the analysis of phospho-p53 (S15) by flow cytometry and the cell cycle by NucleoCounter ® NC-250™. Cell-based assays were also assessed on the proteasome activity and on the ROS generation. To further evaluate the apoptotic mechanism at the molecular level, proteomic profiling was conducted. The current presentation was supported by the ÚNKP-19-3-I-SE-49 New National Excellence Program of the Ministry for Innovation and Technology.
Results: At first, the cytotoxicity inhibiting effect of alpha-lipoic acid was proved in melanoma cells. Analysis of p53 phosphorylation and the cell cycle progression revealed that ALA failed to counteract the effects of BOZ on these processes. Nevertheless, a good correlation was found between the inhibition of the cytotoxicity, the anti-proteasome activity and the oxidative stress level after the co-treatment with 20 ng/mL BOZ + 100 g/mL ALA. Downregulation of apoptotic proteins such as HO-1 and Claspin along with the inhibition of the cleavage of Caspase-3 indicated the proteomic background of the altered responsiveness of the melanoma cells exposed to BOZ + ALA.
Conclusions: The antagonizing effect of ALA on the antineoplastic activity of BOZ in melanoma cells draw the attention to the proper application of cancer supportive care.

Additional Information

László Kőhidai
kohlasz2@gmail.com

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

2925

Start

12:59

End

13:02

Authors (legacy)

Takács, A.1; Lajkó, E.1; Láng, O.1; Istenes, I.1; Kőhidai, L.1

1 Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary
2 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary