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Ruthana date extract inhibited proliferation of human hepatocellular carcinoma (HepG2) cells by modulation of BAX gene

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Abstract

Cancer response to chemotherapeutic agents and its side effects remain a challenge for the development of new anticancer compounds. Dates are consumed worldwide due to their high nutritional value. We investigated the cytotoxicity and expression of the proapoptotic BAX gene in human hepatocellular carcinoma (HepG2) cells treated with Ruthana date ethanolic extract (RDE). The RDE ingredients analyzed by GC/MS and HepG2 cells were treated with different concentrations of RDE for 24, 48, and 72 h. Cytotoxicity, cell viability, DNA fragmentation, and BAX expression were determined. The GC/MS analysis of RDE showed its high content of quercetin, myricetin kaempferol, thymine, and catechol as the most active ingredients. HepG2 treated with RDE showed a significant change in morphological characteristics related to cell death. The antiproliferative activity determined by WST-1 demonstrated that RDE significantly reduced cell viability. Cells treated with RDE (10–60 mg) showed gradual DNA fragmentation in a dose-dependent manner. Gene expression analysis showed upregulation of BAX at 30 mg/ml of RDE (p < 0.001). However, it showed downregulation at (40–60 mg/ml) as compared to control. Our findings indicated that RDE exert cytotoxicity against HepG2 cells due to its high content of flavonoids. This effect through DNA fragmentation and activation of the proapoptotic BAX gene.

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All datasets generated or analyzed during this study are included in the manuscript.

Abbreviations

RDE:

Ruthana Date extract

GC/MS:

Gas chromatography/mass spectrum

HCC:

Hepatocellular carcinoma

HepG2:

Hepatocellular carcinoma cell line

WST-1:

(2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt

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Acknowledgements

This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz, University, Jeddah, under grant no. (RG-24-130-42). The authors, therefore, acknowledge with thanks DSR for technical and financial support.

Funding

This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz, University, Jeddah, under grant no. (RG-24–130-42).

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia

    Etimad Huwait, Seham M. Awaji, Taha A. Kumosani & Khalid O. Abulnaja

  2. Production of Natural Products For Industrial Purposes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia

    Taha A. Kumosani

  3. Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia

    Taha A. Kumosani, Elie K. Barbour & Khalid O. Abulnaja

  4. R and D Department, Opticon Hygiene Consulting, 78807, Oechsli, Switzerland

    Elie K. Barbour

  5. Bioactive Natural Products Research Group, King Abdulaziz University, Jeddah, Saudi Arabia

    Khalid O. Abulnaja

  6. Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt

    Said S. Moselhy

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  1. Etimad Huwait
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  2. Seham M. Awaji
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  3. Taha A. Kumosani
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  4. Elie K. Barbour
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  5. Khalid O. Abulnaja
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  6. Said S. Moselhy
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Contributions

TAK, SSM: design protocol; EHH and SMA: running experiments, EKB and KOA and SM: analyzed data and interpretations. ALL authors revise the manuscript and approve it.

Corresponding author

Correspondence to Said S. Moselhy.

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The study protocol was approved by the Ethics Committee of King Abdulaziz University Hospital, Jeddah, Saudi Arabia. The protocol was done according to the ethical guidelines of the 1975 Declaration of Helsinki.

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Huwait, E., Awaji, S.M., Kumosani, T.A. et al. Ruthana date extract inhibited proliferation of human hepatocellular carcinoma (HepG2) cells by modulation of BAX gene. Environ Sci Pollut Res 29, 63369–63378 (2022). https://doi.org/10.1007/s11356-022-20240-y

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