Bioactivity Studies of Hesperidin and XAV939

Ahmed E Fazary; Mohammad Y Alfaifi; Serag Eldin I Elbehairi; Mohamed E Amer; Mohamed S M Nasr; Tamer M M Abuamara; Doaa A Badr; Yi-Hsu Ju; Aly F Mohamed

doi:10.1021/acsomega.1c03080

Bioactivity Studies of Hesperidin and XAV939

ACS Omega. 2021 Jul 26;6(30):20042-20052. doi: 10.1021/acsomega.1c03080. eCollection 2021 Aug 3.

Authors

Ahmed E Fazary^{1

2}, Mohammad Y Alfaifi³, Serag Eldin I Elbehairi^{3

4}, Mohamed E Amer⁵, Mohamed S M Nasr⁶, Tamer M M Abuamara⁶, Doaa A Badr¹, Yi-Hsu Ju⁷, Aly F Mohamed⁸

Affiliations

¹ Applied Research Department, Research and Development Sector, Egyptian Organization for Biological Products and Vaccines (VACSERA Holding Company), 51 Wezaret El-Zeraa St., Agouza, Giza 12654, Egypt.
² National Committee for Pure and Applied Chemistry (NCPAC 2018-2022), Academy of Scientific Research and Technology (ASRT), 110 Al Kasr Al Aini, El-Sayeda Zainab, Cairo Governorate 11334, Egypt.
³ Department of Biology, Science Collage, King Khalid University, Abha 9004, Saudi Arabia.
⁴ Cell Culture Laboratory, Research and Development Sector, Egyptian Organization for Biological Products and Vaccines (VACSERA Holding Company), 51 Wezaret El-Zeraa St., Agouza, Giza 12654, Egypt.
⁵ Histology Department, Faculty of Medicine, Al-Azhar University, Damietta, P.C. 34511, Egypt.
⁶ Histology Department, Faculty of Medicine, Al-Azhar University, Nasr City, Cairo 11884, Egypt.
⁷ Graduate Institute of Applied Science and Technology, Department of Chemical Engineering, Taiwan Building Technology Center, National Taiwan University of Science and Technology, 43 Section 4, Keelung Road, Taipei 10607, Taiwan.
⁸ The International Center for Advanced Researches (ICTAR-Egypt), Cairo 307422, Egypt.

Abstract

The present work aimed to evaluate the reactivity of natural bioflavonoid hesperidin (HSP) and synthetically derived XAV939 (XAV) against human hepatocellular carcinoma (HepG2), human breast cancer (MDA-MB231) cancer cell lines, and related molecular and pathological profiles. Data recorded revealed that the cytotoxic potential of the tested products was found to be cell type- and concentration-dependent. The half-maximal inhibitory concentration (IC₅₀) value of the HSP-XAV mixture against MDA-MB231 was significantly decreased in the case of using the HSP-XAV mixture against the HepG2 cell line. Also, there was a significant upregulation of the phosphotumor suppressor protein gene (P53) and proapoptotic genes such as B-cell lymphoma-associated X-protein (Bax, CK, and Caspase-3), while antiapoptotic gene B-cell lymphoma (Bcl-2) was significantly downregulated compared with the untreated cell control. The cell cycle analysis demonstrated that DNA accumulation was detected mainly during the G2/M phase of the cell cycle accompanied with the elevated reactive oxygen species level in the treatment of HepG2 and MDA-MB231 cell lines by the HSP-XAV mixture, more significantly than that in the case of cell control. Finally, our finding suggests that both HSP and XAV939 and their mixture may offer an alternative in human liver and breast cancer therapy.