Integrative In Vitro and In Silico Evaluation of Etlingera hemisphaerica Reveals Potent Estrogen Receptor–Targeted Cytotoxicity Against MCF-7 Breast Cancer Cells

نویسندگان

1 Department of Biology Education, Faculty of Teacher Training and Education, Universitas Serambi Mekkah. Jl. Tgk. Imum Lueng Bata, Banda Aceh 23245, Aceh, Indonesia

2 Master of Biology Education, Graduate School, Universitas Serambi Mekkah. Jl. Tgk. Imum Lueng Bata, Banda Aceh 23245, Aceh, Indonesia

3 Department of Biology Education, Faculty of Teacher Training and Education, Universitas Serambi Mekkah. Jl. Tgk. Imum Lueng Bata, Banda Aceh 23245, Aceh, Indonesia

4 Faculty of Health Science and Technology, Universitas Jenderal Achmad Yani, Cimahi, Indonesia

5 Department of Psychology and Nursing, Faculty of Medicine, Universitas Malikussaleh. Jl. Cot Tengku Nie Reuleut, Aceh Utara 24353, Aceh, Indonesia

doi
10.48309/ajca.2026.566349.2005
چکیده

Breast cancer remains a leading cause of cancer-related mortality worldwide, emphasizing the need for effective and affordable therapeutic agents derived from natural sources. Etlingera hemisphaerica, a member of the Zingiberaceae family, has received limited scientific attention despite its recognized ethnopharmacological relevance. This study aimed to investigate the anticancer potential of E. hemisphaerica through an integrated in vitro cytotoxicity and in silico molecular modeling approach. The cytotoxic activity of the ethanol extract of E. hemisphaerica was evaluated against estrogen receptor-positive (ERα⁺) MCF-7 human breast cancer cells using the MTT assay after 72 h of exposure. The extract exhibited a pronounced dose-dependent reduction in cell viability, yielding an exceptionally low IC₅₀ value of 1.16 ppm, categorizing it as highly cytotoxic according to established screening criteria. Dose–response modeling using a four-parameter log-logistic regression confirmed a classical sigmoidal inhibition pattern, indicative of a specific and saturable biological effect. To elucidate potential molecular mechanisms, major flavonoid constituents were subjected to molecular docking analysis against estrogen receptor alpha (ERα). Several compounds, particularly quercetin, luteolin, isorhamnetin, and kaempferol, exhibited strong binding affinities (ΔG ≤ −8.4 kcal/mol), comparable to known ERα modulators. Drug-likeness and ADMET profiling further revealed that quercetin exhibits favorable pharmacokinetic properties, including high gastrointestinal absorption, non-P-glycoprotein substrate behavior, and full compliance with Lipinski’s rule of five. Collectively, these findings indicate that E. hemisphaerica possesses potent cytotoxic activity against breast cancer cells, potentially mediated through modulation of ERα-related signaling pathways and mitochondrial-dependent mechanisms. This integrative study provides the first mechanistic insight into its anticancer potential and supports its promise as a valuable source of lead compounds for breast cancer drug discovery.