Multi-target Mechanisms of Moringa oleifera Stem Bark Compounds against Luminal A Breast Cancer: Integrative In silico and In vitro Analyses
Fitrah Pratama Amiruddin, Ika Yustisia, Syahrijuita Kadir, Marhaen Hardjo, Gita Vita SorayaIntroduction:
Luminal A Breast Cancer (LABC) remains a pressing global health concern. Natural products have been widely explored as alternative anticancer agents. Moringa oleifera L. has demonstrated anticancer potential; however, studies on its stem bark are limited.
Methods:
M. oleifera Stem Bark (MO extract was analyzed by GC-MS, and identified compounds were subjected to in silico evaluation using ADMET, PASS, and SwissTargetPrediction. Network pharmacology and UALCAN (TCGA-BRCA) were utilized to validate the expression of hub genes. Cytotoxicity against MCF-7 cells was assessed using the MTT assay, and the IC₂⁽ was determined via four-parameter logistic (4PL) regression.
Results:
Twenty bioactive main compounds were discovered, including steroids (D-Homoestra- 1,3,5(10),8(14)-tetraen-17-one), terpenoids (1H-3a,6-Methanoazulene-3-carboxylic acid methyl ester), and retinoids (9-cis-Retinal). Eight key targets (STAT3, HSP90AA1, BCL2, GAPDH, PPARG, PTGS2, EGFR, and IL1B) were enriched in key oncogenic pathways involved in enhanced proliferation, reduced apoptosis, active metabolism, and lower inflammatory and differentiation signaling. The extract inhibited MCF-7 viability from 19.8% (3.9 μg/mL) to 83.4% (250 μg/mL), with an IC50 of 42.8 μg/mL (R² = 0.9805). Morphological changes suggestive of apoptosis are characterized by cell shrinkage and detachment.
Discussion:
The multi-target profile of MOSB points to coordinated modulation of proliferative, anti-apoptotic, metabolic, and inflammatory pathways in LABC cells. The observed cytotoxicity (IC50: 42.8 μg/mL) and apoptotic morphology support the network pharmacology predictions, indicating combined effects of the bioactive compounds.
Conclusions:
MOSB ethanolic extract exhibits antiproliferative activity against LABC and may involve multi-target modulation, supporting its potential for further in vivo and mechanistic validation.