Combined effects of senexin B and antitumour agents on neuroblastoma and glioblastoma cell lines

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Abstract

Neurogenic tumors such as neuroblastoma and glioblastoma are highly heterogeneous and particularly aggressive: they are characterized by rapid growth, metastasis and resistance to treatment. Both tumors exhibit MYCN oncogene copy-number disruption, impaired gene transcription, and overall high transcriptional deregulation. In this study, we evaluated the survival of glioblastoma and neuroblastoma cells and performed real-time PCR analysis to assess the change in expression of MYCN, HAND2, PHOX2A, and PHOX2B oncogenes after exposure to senecin B in combination with temozolomide and the potential therapeutic agent 10058-F4. As a result, a trend of increased PHOX2B gene expression and decreased PHOX2A gene expression after drug exposure was observed in one of the neuroblastoma lines and both glioblastoma lines, an increase in MYCN and HAND2 gene expression was also observed. Viability tests showed that substance 10058-F4 was effective against neuroblastoma line but not glioblastoma lines. However, senexin B enhanced the inhibitory effect of 10058-F4 on glioblastoma cell lines and also enhanced the effect of temozolomide on the T98G cell line.

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About the authors

D. V. Mazur

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, RAS

Email: nadine.antipova@gmail.com
Russian Federation, ul. Miklukho-Maklaya 16/10, Moscow, 117997

S. S. Pogodaeva

ITMO University

Email: nadine.antipova@gmail.com
Russian Federation, Kronverksky prosp. 49, liter A, St. Petersburg, 197101

O. A. Kuchur

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, RAS; ITMO University

Email: nadine.antipova@gmail.com
Russian Federation, ul. Miklukho-Maklaya 16/10, Moscow, 117997; Kronverksky prosp. 49, liter A, St. Petersburg, 197101

O. O. Miletina

ITMO University

Email: nadine.antipova@gmail.com
Russian Federation, Kronverksky prosp. 49, liter A, St. Petersburg, 197101

A. I. Rezekina

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, RAS

Email: nadine.antipova@gmail.com
Russian Federation, 117997 Москва, улица Миклухо-Маклая, 16/10

E. G. Petrosyan

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, RAS

Email: nadine.antipova@gmail.com
Russian Federation, ul. Miklukho-Maklaya 16/10, Moscow, 117997

D. A. Rudik

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, RAS

Email: nadine.antipova@gmail.com
Russian Federation, ul. Miklukho-Maklaya 16/10, Moscow, 117997

Е. I. Ivanova

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, RAS

Email: nadine.antipova@gmail.com
Russian Federation, ul. Miklukho-Maklaya 16/10, Moscow, 117997

А. А. Shtil

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, RAS; N.N. Blokhin National Medical Research Centre for Oncology

Email: nadine.antipova@gmail.com
Russian Federation, ul. Miklukho-Maklaya 16/10, Moscow, 117997; Kashirskoye shosse 23, Moscow, 115522

N. V. Antipova

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, RAS; National Research University “Higher School of Economics”

Author for correspondence.
Email: nadine.antipova@gmail.com
Russian Federation, ul. Miklukho-Maklaya 16/10, Moscow, 117997; ul. Profsoyuznaya 33/4, Moscow, 101000 Russia

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2. Fig. 1. Survival (% of cells) of GBM (a–g) and NB (d–f) lines after 72-hour incubation with 10058-F4 and TMZ. Survival values ​​in the control are taken as 100%.

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3. Fig. 2. Relative expression of supertarget genes in NB (a, b) and GBM (c, d) cell lines after 24 h of incubation. Concentrations: 10058-F4 – 40 μM, TMZ – 50 (NB) and 250 μM (GBM); SenB – 1 μM 1 h before addition of other compounds. Average values ​​(relative to the PCR amplification product of 18S RNA) and standard deviations from the results of three independent measurements are shown.

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4. Fig. 3. Survival (in % of cells) after 24-h incubation of NB (a, b) and GBM (c, d) cell lines with substances and their combinations. The substances were added in the following concentrations: 10058-F4 – 40 μM, TMZ – 50 (NB) and 250 μM (GBM); SenB – 1 μM 1 h before the other substances. *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001.

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