The Potential of Eleutherine bulbosa in Inducing Apoptosis and Inhibiting Cell Cycle in Breast Cancer: A Network Pharmacology Approach and In Vitro Experiments.

OBJECTIVE: The objective of this study was to evaluate the potential and mechanisms of phytochemicals in Eleutherine bulbosa (EBE) in inducing apoptosis and inhibiting the cell cycle in breast cancer through a network pharmacology approach and in vitro validation. METHODS: This research employed a literature review approach to identify active anti-cancer compounds and utilized a network pharmacology approach to predict the mechanisms of action of EBE compounds in breast cancer. In addition, in vitro experiments were conducted using MTT method to evaluate the effects of EBE on the cytotoxicity of T47D cells, and the flow cytometry method was employed to determine the impact of EBE on apoptosis and the cell cycle. RESULTS: The network pharmacology analysis revealed that EBE had an impact on 42 genes involved in breast cancer, including 23 important target genes implicated in the pathophysiology of breast cancer. Pathway analysis using the KEGG database showed a close association between EBE and crucial signaling pathways in breast cancer, including P53 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, apoptosis and cell cycle. In vitro experiments demonstrated that EBE exhibited moderate anti-cancer activity. Furthermore, EBE demonstrated significant potential in inducing apoptosis in breast cancer cells, with a percentage of apoptotic cells reaching 93.6%. Additionally, EBE was observed to disrupt the cell cycle, leading to a significant increase in the sub G1 and S phases, and a significant decrease in the G2-M and G1 phases. CONCLUSION: EBE has the potential to be an anti-cancer agent through various mechanisms, including apoptosis induction and cell cycle inhibition in breast cancer cells. These findings provide new insights into the potential of EBE as an alternative treatment for breast cancer.

Effect of ethanol extract from Chrysanthemum cinerariifolium leaves on Ki-67 proliferation and dysplasia severity in a rat model of oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is a malignant tumor that can rapidly infiltrate the oral epithelial tissue and cause high mortality worldwide because the available therapies are less effective. Chrysanthemum cinerariifolium leaf contains secondary metabolites as anti-inflammatory, antioxidant, anticancer, and antimutagenic. Aims: The study aimed to analyze the ethanolic extract of C. cinerariifolium leaf in reducing proliferation (Ki-67) and the degree of dysplasia in OSCC rats. Methods: This study used male Sprague Dawley induced by 7,12-dimethylbenz(a)anthracene (DMBA) 0.5% and divided into five treatment groups, namely positive control/C+ (sick), negative control/C- (healthy), and treatment group induced with DMBA and given extract C. cinerariifolium leaf with successive doses of T1, T2, and T3 (50, 100, and 200 mg/kg bw). The oral epithelium was stained with hematoxylin and eosin and immunohistochemically stained with a Ki-67 monoclonal antibody. The statistical analysis utilizes the one-way analysis of variance test. Results: The results showed that T1 at a dose of 200 mg/kg bw could significantly reduce Ki-67 expression and the degree of oral epithelial dysplasia (OED; p < 0.05) close to healthy controls. Conclusion: The conclusion shows that C. cinerariifolium leaf extract can be a therapy against OSCC by decreasing cell proliferation and the degree of OED.

Activity and Toxicity of Eleutherine palmifolia (L.) Merr. Extract on BALB/c Mice Colitis-Associated Colon Cancer Model.

OBJECTIVE: Eleutherine palmifolia (L.) Merr. extract (EPE) containing isoliquiritigenin and oxyresveratrol is believed to be an anticancer agent. This study evaluates colon histopathology, TNF-α, TGF-ß, and hepatotoxicity on BALB/c mice colitis-associated colon cancer (CAC) model treated with EPE. METHODS: In vivo study was performed on BALB/c mice CAC model induced by 10 mg/kgBW AOM on the first day followed by administration that each cycle consisted of 5% DSS in water for seven days and regular water for seven days. The indicators of the formation of CAC were observed by a fecal occult blood test (FOBT) and serum amyloid α (SAA) test. The treatment was conducted once a week started from the seventh week up to the twentieth week with six treatment groups: I was administrated by regular water only (negative control), II was administrated by AOM and DSS only (positive control), III was administrated by doxorubicin,  IV-VI were treated by EPE (0.25 mg/kg BW, 0.50 mg/kg BW, and 1.00 mg/kg BW) respectively. The colon and liver's histopathology was observed using hematoxylin-eosin (HE) staining, TNF-α with immunohistochemistry (IHC), and level measurement of TGF-ß colon with ELISA reader. The data were used one-way ANOVA followed by post hoc as statistical analysis. RESULTS: The administration of EPE increased the expression of TNF-α, the total of goblet cells of the colon, and decreased the level of TGF-ß. Administration of EPE 0.50 mg/20g BW decreased a liver histopathological score but induced a histopathological alteration of the liver at a dose of 1.00 mg/20g BW. CONCLUSION: This study indicate that EPE could be recommended as a colon anticancer through increase the goblet cells, induce apoptosis through increase TNF-α, and decrease TGF-ß.