Enhancement of apoptosis in HCT116 and HepG2 cells by Coix lacryma-jobi var. lacryma-jobi seed extract in combination with sorafenib.
10.1016/j.chmed.2025.02.005
- Author:
Supawadee PARHIRA
1
;
Guoyuan ZHU
2
;
Apirath WANGTEERAPRASERT
3
;
Suphunwadee SAWONG
4
;
Pennapha SUKNOPPAKIT
4
;
Julintorn SOMRAN
5
;
Naphat KAEWPAENG
6
;
Khemmachat PANSOOKSAN
6
;
Dumrongsak PEKTHONG
6
;
Piyarat SRISAWANG
6
Author Information
1. Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.
2. State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa 999078, Macau.
3. Department of Medicine, Faculty of Medicine, Naresuan University, Phitsanulok 65000, Thailand.
4. Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand.
5. Department of Pathology, Faculty of Medicine, Naresuan University, Phitsanulok 65000, Thailand.
6. Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand.
- Publication Type:Journal Article
- Keywords:
Coix lacryma-jobi var. lacryma-jobi;
HCT116;
HepG2;
PI3K/AKT/mTOR pathway;
apoptosis;
reactive oxygen species;
seed extracts;
sorafenib
- From:
Chinese Herbal Medicines
2025;17(2):322-339
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:Coix lacryma-jobi, a highly regarded Asian herb widely used in traditional Chinese medicine, is recognized for its dual benefits in promoting overall health and treating various diseases. While it exhibits moderate anticancer efficacy when used alone, this study investigated the enhanced anticancer potential of raw and cooked Coix lacryma-jobi var. lacryma-jobi (CL) seed extracts in combination with sorafenib against HCT116 and HepG2 cancer cell lines. The combination of sorafenib with other anticancer agents, including natural extracts, has garnered significant attention as a promising strategy for developing more effective cancer therapies.
METHODS:Dry powders of raw (R) and cooked (C) CL seeds, obtained from a local commercial source in Thailand, were extracted and fractionated using ethanol (E), dichloromethane (D), ethyl acetate (A), and water (W) to produce eight fractions: CLRE, CLCE, CLRD, CLCD, CLRA, CLCA, CLRW, and CLCW. The coixol content in raw and cooked seed extracts was quantified and expressed as μg of coixol per gram of extract. The cytotoxic effects of these fractions were evaluated against HCT116 and HepG2 cells using the MTT assay. Fractions demonstrating the most significant cytotoxic responses were combined with sorafenib to evaluate their synergistic effects. Apoptosis induction and mitochondrial membrane potential (MMP) were assessed, and the underlying mechanism of apoptosis was explored by analyzing reactive oxygen species (ROS) generation and antioxidant protein expression levels. Additionally, the combination treatment's effect on the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway was investigated.
RESULTS:One gram of CLCE and CLCD extracts contained higher coixol levels (7.02 μg and 9.69 μg, respectively) compared to CLRE and CLRD (2.66 μg and 5.96 μg, respectively). Coixol content in CLRA, CLRW, and CLCW fractions was undetectable under the study conditions. All extract fractions exhibited IC50 values exceeding 1 mg/mL after 24- and 48-hour incubations with HCT116 and HepG2 cells, indicating limited cytotoxicity when used independently. CLRD and CLCD fractions were selected for combination studies at a concentration of 1 mg/mL, combined with sub-IC50 concentrations of sorafenib to minimize its side effects. This combination significantly increased cytotoxicity, inducing apoptosis in HCT116 and HepG2 cells by elevating ROS levels and reducing the expression of superoxide dismutase 2 and catalase. Furthermore, the combination treatment downregulated the PI3K/AKT/mTOR pathway, indicating a targeted anticancer mechanism.
CONCLUSION:The combination of CLCD with sorafenib demonstrates significant potential as a strategy for future anticancer therapies. This CL seed extract, cultivated and commercially available in Thailand, shows promise as a natural supplement to enhance the efficacy of chemotherapy in upcoming clinical anticancer applications.
