Calotropis gigantea stem bark extract activates HepG2 cell apoptosis through ROS and its effect on cytochrome P450
Pennapha Suknoppakit,
Apirath Wangteeraprasert,
Orakot Simanurak,
Julintorn Somran,
Supawadee Parhira,
Dumrongsak Pekthong,
Piyarat Srisawang
Affiliations
Pennapha Suknoppakit
Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand
Apirath Wangteeraprasert
Department of Medicine, Faculty of Medicine, Naresuan University, Phitsanulok 65000, Thailand
Orakot Simanurak
Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand
Julintorn Somran
Department of Pathology, Faculty of Medicine, Naresuan University, Phitsanulok, 65000, Thailand
Supawadee Parhira
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand; Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand; Center of Excellence for Environmental Health and Toxicology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand
Dumrongsak Pekthong
Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand; Center of Excellence for Environmental Health and Toxicology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand; Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand; Corresponding author. Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand.
Piyarat Srisawang
Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand; Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand; Center of Excellence in Medical Biotechnology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand; Corresponding author. Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand.
The 95% ethanolic extract of the dry powder of Calotropis gigantea (C. gigantea) stem bark was separated by fractionation with different solutions to yield 4 fractions: dichloromethane (CGDCM), ethyl acetate (CGEtOAc), and water (CGW). This research focused on CGDCM-induced apoptosis in HepG2 cells with IC50 and above-IC50 values, which provide useful information for future anticancer applications. CGDCM had lower cytotoxicity on normal lung fibroblast IMR-90 cells than on HepG2 cells. Apoptotic induction of CGDCM was mediated by decreased fatty acid and ATP synthesis while increasing reactive oxygen species production. The effects of the four extracts on the activity of the four major CYP450 isoforms (CYP1A2, CYP2C9, CYP2E1 and CYP3A4) were determined using the CYP-specific model activity of each isoform. All four fractions of the extract were shown to be poor inhibitors of CYP1A2 and CYP2E1 (IC50 > 1000 μg/mL) and moderate inhibitors of CYP3A4 (IC50 = 56.54–296.9 μg/mL). CGDCM and CGW exerted moderate inhibition activities on CYP2C9 (IC50 = 59.56 and 46.38 μg/mL, respectively), but CGEtOH and CGEtOAc exhibited strong inhibition activities (IC50 = 12.11 and 20.43 μg/mL, respectively). It is proposed that C. gigantea extracts at high doses have potential for further studies to develop alternative anticancer applications. Inhibiting CYP2C9 activity may also lead to drug-herb interactions.
