Abstract
Lung cancer is the most common cause of cancer-related mortality, chemo-resistance, and toxicity limit treatment. The focus is on innovative combined phytotherapy to improve treatment outcomes. Our aim was to investigate the potential effects of daidzein nanosuspension (DZ-NS) and its combination with cisplatin (CIS) on A549 non-small lung cancer cells. Cytotoxicity was investigated using MTT and Chou-Talalay methods. Oxidative, apoptotic, and inflammatory markers were analyzed by ELISA and qRT-PCR. The IC50 value for DZ-NS was 25.23 µM for 24 h and was lower than pure DZ (IC50 = 835 µM for pure DZ). DZ-NS (at IC50x2 and IC50 values) showed synergistic cytotoxicity with CIS. The cells treated with DZ-NS had low TOS and OSI levels. However, DZ-NS failed to regulate Cas3 and TGF-β1 activation in A549 cells. MMP-9 gene expression was significantly suppressed in DZ-NS-treated cells, especially in combination therapy. DZ represents a potential combination option for the treatment of lung cancer, and its poor toxicokinetic properties limit its clinical use. To overcome these limitations, the effects of the nanosuspension formulation were tested. DZ-NS showed a cytotoxic effect on A549 cells and optimized the therapeutic effect of CIS. This in vitro synergistic effect was mediated by suppression of MMP-9 and not by oxidative stress or Cas3-activated apoptosis. This study provides the basis for an in vivo and clinical trial of DZ-NS with concurrent chemotherapy.
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Data availability
Data available on request from the authors. The data that support the findings of this study are available from the corresponding author, Merve Becit-Kizilkaya, upon reasonable request.
Abbreviations
- Cas-3:
-
Caspase-3
- CI:
-
Combination index
- CIS:
-
Cisplatin
- DZ-NS:
-
Daidzein nanosuspension
- DZ:
-
Daidzein
- ELISA:
-
Enzyme-linked immunosorbent assay
- MMP:
-
Matrix metalloproteinase-9
- MTT:
-
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
- NS:
-
Nanosuspension formulations
- NSCLC:
-
Non-small cell lung cancer
- OSI:
-
Oxidative stress index
- qRT-PCR:
-
Quantitative real time polymerase chain reaction
- TAS:
-
Total antioxidant status
- TGF-β1:
-
Transforming growth factor-β1
- TOS:
-
Total oxidant status
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The authors thank Afyonkarahisar Health Sciences University Scientific Research Projects Coordination Unit for financial support.
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This study was supported by Afyonkarahisar Health Sciences University Scientific Research Projects Coordination Unit under grant number 22.GENERAL.009.
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All authors contributed to the study conception and design. Material preparation by [Afife Busra Ugur-Kaplan] and [Meltem Cetin], data collection and analysis were performed by [Seyma Oncu], [Merve Becit-Kizilkaya], [Serkan Sen] and [Sefa Celik]. The first draft of the manuscript was written by [Seyma Oncu] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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Oncu, S., Becit-Kizilkaya, M., Sen, S. et al. Daidzein nanosuspension in combination with cisplatin to enhance therapeutic efficacy against A549 non-small lung cancer cells: an in vitro evaluation. Naunyn-Schmiedeberg's Arch Pharmacol 397, 4871–4881 (2024). https://doi.org/10.1007/s00210-023-02924-5
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DOI: https://doi.org/10.1007/s00210-023-02924-5