The Antioxidant from Ethanolic Extract ofFruits Activates Phosphatase and Tensin Homolog In Vitro and In Vivo: A New Insight on Its Antileukemic Effect.
Int J Mol Sci. 2019 Apr 19 ;20(8). Epub 2019 Apr 19. PMID: 31010164
Tratt is a Chinese herbal remedy that is used in the treatment of diarrhea, burns, rheumatoid arthritis, and hemorrhage. Despite its use in Asian folk medicine, there are limited reports on the biological activity offruits. This study focused on the investigation of the antitumor effect of the antioxidative ethanolic extract offruits (RCE) along with its underlying mechanism of action. RCE showed a potent cytotoxic effect against Sup-T1 and Molt-4 lymphoblastic leukemia cells. In the xenograft animal model, the tumor size was significantly reduced to about 59.42% in the RCE-treated group in comparison with the control group. The use of RCE (37.5, 75, or 150μg/mL) triggered apoptosis by 26.52-83.49%, disrupted mitochondrial membrane potential (MMP) by 10.44-58.60%, and promoted calcium release by 1.29-, 1.44-, and 1.71-fold compared with the control group. The extract induced redox oxygen species (ROS) generation through the elimination of Nrf2/Keap1/P62-mediated oxidative stress response. The loss of phosphatase and tensin homolog (PTEN) activation by RCE impaired PI3K/Akt/Foxo and Jak/Stat activation pathways, which contributed to tumorigenesis. These multiple targets ofagainst hematologic cancer cells suggested its potential application as an antileukemic dietary supplement.