{"doi":"10.3390/ijms23052887","title":"Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis","abstract":"Aromatase inhibitors (AIs) are standard treatment for estrogen-dependent postmenopausal breast tumors; however, resistance develops leading to tumor relapse and metastasis. We previously demonstrated that glyceollin inhibits proliferation, survival, and migration of hormone-independent letrozole-resistant breast cancer. Since many AI-resistant tumors remain hormone-dependent, identifying distinctions between estrogen-receptor-positive (ER+) and ER-negative (ER-) AI-resistant tumor response to therapy is critical. We hypothesize that treating ER+ letrozole-resistant T47D breast cancer cells (T47DaromLR) with a combination of 10 μM glyceollin and 0.5 μM lapatinib (a dual EGFR/HER2 inhibitor) will decrease cell proliferation through induction of apoptosis. The T47DaromLR cells were found to overexpress HER2 and MAPK while maintaining aromatase and ER levels compared to their letrozole-sensitive (T47Darom) counterparts. In the absence of estrogen stimulation, glyceollin ± lapatinib had no effect on the proliferation of the T47Darom cells, while glyceollin treatment caused 46% reduction in the proliferation of T47DaromLR cells, which was further diminished when combined with lapatinib. While neither agent influenced cell migration, glyceollin and lapatinib reduced S and G2/M phase cell entry and exclusively induced apoptosis by 1.29-fold in the T47DaromLR cells. Taken together, these results suggest that glyceollins and lapatinib may have potential as a novel combination therapeutic approach for hormone-dependent, letrozole-resistant tumors.","journal":"International Journal of Molecular Sciences","year":2022,"id":272531,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":528173,"name":"Jankiben Patel","orcid":null,"position":1,"is_corresponding":false},{"id":332034,"name":"Akash Gupta","orcid":"0000-0001-7305-055X","position":2,"is_corresponding":false},{"id":527347,"name":"A. Michael Davidson","orcid":"0000-0002-7831-8532","position":3,"is_corresponding":false},{"id":383495,"name":"Christopher Williams","orcid":"0000-0001-8896-0978","position":4,"is_corresponding":false},{"id":939083,"name":"Florastina Payton‐Stewart","orcid":"0000-0002-0677-8150","position":5,"is_corresponding":false},{"id":939084,"name":"Stephen M. Boué","orcid":"0000-0002-2790-4427","position":6,"is_corresponding":false},{"id":376497,"name":"Matthew E. Burow","orcid":"0000-0002-0642-6630","position":7,"is_corresponding":false},{"id":939569,"name":"Rahul Khupse","orcid":null,"position":8,"is_corresponding":false},{"id":527349,"name":"Syreeta L. Tilghman","orcid":"0000-0003-3215-1252","position":9,"is_corresponding":false},{"id":528172,"name":"Rashidra R. Walker","orcid":null,"position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T00:27:47.926496Z","pmid":"35270029","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}