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Design and cytotoxic evaluation via apoptotic and antiproliferative activity for novel 11(4-aminophenylamino)neocryptolepine on hepatocellular and colorectal cancer cells

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Abstract

The current study evaluated the cytotoxic activity of 11(4-Aminophenylamino)neocryptolepine (APAN), a novel derivative of neocryptolepine, on hepatocellular (HepG2) and colon (HCT-116) carcinoma cell lines as well as, the possible molecular mechanism through which it exerts its cytotoxic activity. The APAN was synthesized and characterized based on their spectral analyses. Scanning for anticancer target of APAN by Swiss software indicated that APAN had highest affinity for protein tyrosine kinase 6 enzyme. Furthermore, Super pred software indicated that APAN can be indicated in hepatic and colorectal cells with 92%. Molecular docking studies indicated that the binding affinity scores of APAN for protein PDB code: 6CZ4 of tyrosine kinase 6 recorded of − 6.6084 and RMSD value of 0.8891°A, while that for protein PDB: 7JL7 of caspase 3 was − 6.1712 and RMSD of 0.8490°A. Treatment of HepG2 and HCT-116 cells with APAN induced cytotoxicity with IC50 of 2.6 and 1.82 μg/mL respectively. In addition, it induced injury and serious morphological changes in cells including, disappearance of microvilli, membrane blebbing, cytoplasmic condensation, and shrunken nucleus with more condensed chromatin. Moreover, APAN significantly increased protein expression of annexin V (apoptotic marker). Furthermore, APAN significantly increased protein expression of caspase 3 and P53. However, it significantly reduced secretion of VEGF protein into the medium and decreased protein expression of PCNA and Ki67 in HepG2 and HCT-116 cells. This study indicated that APAN had cytotoxic activity against HepG2 and HCT-116 cells via increasing the expression of apoptotic proteins and reducing the expression of proliferative proteins.

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Data availability

All data used in this study are included in this published article.

Abbreviations

APAN:

11(4-AminoPhenylamnio)neocryptolepine

DMF:

Dimethyl formamide

HepG2:

Hepatocellular carcinoma

HCT-116:

Colorectal carcinoma

SRB:

Sulforhodamine (B)

PCNA:

Proliferation cell nuclear antigen

VEGF:

Vascular endothelial growth factor

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Acknowledgements

The authors acknowledge funding from Princess Nourah bint Abulrahman University Researchers Supporting Project number (PNURSP2022R164), Princess Nourah bint Abulrahman University, Riyadh, Saudi Arabia.

Funding

This work was funded by Princess Nourah bint Abulrahman University Researchers Supporting Project Number (PNURSP2022R164), Princess Nourah bint Abulrahman University, Riyadh, Saudi Arabia.

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Authors and Affiliations

  1. Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom, 32511, Egypt

    Esraa Tariq Nagy, Abdullah A. S. Ahmed, Ibrahim El Tantawy El Sayed & Ahmed A. El-Gokha

  2. Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, 84428, Saudi Arabia

    Elshaymaa I. Elmongy

  3. Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo, Egypt

    Saad M. EL-Gendy

  4. Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt

    Ibrahim Elmadbouh

  5. Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Menoufia University, Sheben Elkom, 32511, Menoufia, Egypt

    Mabrouk Attia Abd Eldaim

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  1. Esraa Tariq Nagy
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  3. Elshaymaa I. Elmongy
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Contributions

ETN, MAAE, AAEG and SMEG suggested the idea and the experimental design; ETN, ASA, EE, IE, EEES performed the experiment and wrote the draft of manuscript with the support of and MAAE; MAAE, EEES and SMEG supervised the implementation of the experiment and analyzed the results. All authors discussed the results and contributed to finalize the manuscript.

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Correspondence to Mabrouk Attia Abd Eldaim.

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Nagy, E.T., Ahmed, A.A.S., Elmongy, E.I. et al. Design and cytotoxic evaluation via apoptotic and antiproliferative activity for novel 11(4-aminophenylamino)neocryptolepine on hepatocellular and colorectal cancer cells. Apoptosis 28, 653–668 (2023). https://doi.org/10.1007/s10495-023-01810-y

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  • DOI: https://doi.org/10.1007/s10495-023-01810-y

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