AL-Ghamdi, Maryam AbduAlsulami, Rawyah RadiBakkar, AshrafKumosani, Taha AbullahBarrbour, Elie KamilAbulnaja, Khalid OmarHuwait, EtimadMoselhy, Said Salama2022-11-112022-11-112022-11https://doi.org/10.1080/14786419.2022.2140803https://bit.ly/3fWPf2xAutophagy is a protective mechanism important in human dis- eases as cancer. We evaluated the impact of khalas date extract (KDE) (20-60 mg/mL) on cell viability, morphological changes, DNA fragmentation and gene expression of LC3B-II associated with autophagosome on HepG2 cell line. The GC/MS identification of KDE showed its high content of flavonoids including quercetin, myricetin, kaempferol and catechol. KDE reduced cell viability of HepG2 with IC50 (31.52 mg/mL). Cells treated with KDE showed two band of DNA fragments at (30 and 40 mg) indicating that KDE induced DNA damage and apoptosis in HepG2. The analysis RT-PCR data showed a 0.2-fold increase in the expression of LC3- B in the cells treated with KDE versus control. We concluded that, KDE flavonoids such as quercetin, myricetin kaempferol exhibited anticancer properties manifested by inhibition of HepG2 cell via- bility and induction of apoptosis and upregulation of the pro- autophagy LC3-B gene. ARTICLE HISTORYen-USKhalas dateflavonoidsautophagycytotoxicityHepG2Articlehttps://doi.org/10.1080/14786419.2022.2140803