Neobavaisoflavone May Modulate the Activity of Topoisomerase Inhibitors towards U-87 MG Cells: An In Vitro Study

Abstract

Despite many advances in therapy, glioblastoma (GB) is still characterized by its poor prognosis. The main reason for this is unsuccessful treatment, which slightly extends the duration of remission; thus, new regimens are needed. One of many types of chemotherapeutics that are being investigated in this field is topoisomerase inhibitors, mainly in combination therapy with other drugs. On the other hand, the search for new anti-cancer substances continues. Neobavaisoflavone (NBIF) is a natural compound isolated from Psoralea corylifolia L., which possesses anti-oxidant, anti-inflammatory, and anti-cancer properties. The aim of this study was to evaluate the effect of NBIF in human U-87 MG glioblastoma cells in comparison to normal human NHA astrocytes, and to examine if it influences the activity of irinotecan, etoposide, and doxorubicin in this in vitro model. We demonstrated that NBIF decreases U-87 MG cells viability in a dose-dependent manner. Furthermore, we found that it inhibits cell growth and causes glutathione (GSH) depletion more intensely in U-87 MG cells than in astrocytes. This study also provides, for the first time, evidence of the potentialization of the doxorubicin effect by NBIF, which was shown by the reduction in the viability in U-87 MG cells.

Chemosensitization of U-87 MG Glioblastoma Cells by Neobavaisoflavone towards Doxorubicin and Etoposide

“…This is consistent with the fact that normal cells are less prone to mitochondrial damage than tumor cells [ 44 ]. On the other hand, the observed effect of NBIF on mitochondria in U-87 MG cells might have contributed to the results that we received previously from the WST-1 test, which is based on the activity of mitochondrial dehydrogenases [ 34 ]. This could be a reason for no differences between the groups treated with etoposide and its mix with the isoflavone.…”

“…In order to investigate the effect of NBIF on the activity of etoposide and doxorubicin in NHA and U-87 MG cells, the assessment of cell number was performed. In the presented experiments, the conditions (concentrations of drugs and the isoflavone, and the time of their exposure to cell cultures) that had been used in our previous study [ 34 ] were applied. The number of cells was estimated using the NucleoCounter ® NC-3000™ fluorescence image cytometer, as described in Section 4.4 .…”

“…The anti-cancer effects of NBIF have been demonstrated in several different tumor cell lines [ 34 , 37 , 38 , 39 , 40 ], including gliomas [ 34 , 38 ]. Previously, we have found that this isoflavone moderately decreased the viability of U-87 MG cells in a concentration-dependent manner, and slightly reduced the percentage of living cells at 100 μM [ 34 ]. We hypothesized that NBIF may affect cell proliferation in a cell cycle-independent manner, as it did not cause cell death.…”

“…According to the literature, doxorubicin or etoposide in combination with polyphenols exert greater anti-tumor effects in the in vitro models [ 28 , 29 , 30 , 31 , 32 , 33 ]. In our previous study [ 34 ], we demonstrated that neobavaisoflavone (NBIF), a Psoralea corylifolia L. polyphenol, has a moderate effect on viability and growth in human U-87 MG glioblastoma cells. Simultaneously, we have also discovered that it increases the impact of doxorubicin on cell viability when combined with it.…”

Computational insights on the antioxidant, antinitrosant, and xanthine oxidase inhibitory capacities of neobavaisoflavone

“…[4][5][6][7][8] Studies have shown that Neo has anti-cancer properties. 4,5,9 It has been shown to inhibit the growth of various cancer cells, including breast cancer, lung cancer, and prostate cancer cells. 4,10 Additionally, Neo has been shown to induce apoptosis in cancer cells, which is an important mechanism for preventing the growth and spread of cancer.…”