{"doi":"10.1111/bph.16497","title":"Blockade of Ca<sub>V</sub>3 calcium channels and induction of G<sub>0</sub>/G<sub>1</sub> cell cycle arrest in colon cancer cells by gossypol","abstract":"Abstract Background and Purpose Gastrointestinal tumours overexpress voltage‐gated calcium (Ca V 3) channels (Ca V 3.1, 3.2 and 3.3). Ca V 3 channels regulate cell growth and apoptosis colorectal cancer. Gossypol, a polyphenolic aldehyde found in the cotton plant, has anti‐tumour properties and inhibits Ca V 3 currents. A systematic study was performed on gossypol blocking mechanism on Ca V 3 channels and its potential anticancer effects in colon cancer cells, which express Ca V 3 isoforms. Experimental Approach Transcripts for Ca V 3 proteins were analysed in gastrointestinal cancers using public repositories and in human colorectal cancer cell lines HCT116, SW480 and SW620. The gossypol blocking mechanism on Ca V 3 channels was investigated by combining heterologous expression systems and patch‐clamp experiments. The anti‐tumoural properties of gossypol were estimated by cell proliferation, viability and cell cycle assays. Ca 2+ dynamics were evaluated with cytosolic and endoplasmic reticulum (ER) Ca 2+ indicators. Key Results High levels of Ca V 3 transcripts correlate with poor prognosis in gastrointestinal cancers. Gossypol blockade of Ca V 3 isoforms is concentration‐ and use‐dependent interacting with the closed, activated and inactivated conformations of Ca V 3 channels. Gossypol and Ca V 3 channels down‐regulation inhibit colorectal cancer cell proliferation by arresting cell cycles at the G 0 /G 1 and G 2 /M phases, respectively. Ca V 3 channels underlie the vectorial Ca 2+ uptake by endoplasmic reticulum in colorectal cancer cells. Conclusion and Implications Gossypol differentially blocked Ca V 3 channel and its anticancer activity was correlated with high levels of Ca V 3.1 and Ca V 3.2 in colorectal cancer cells. The Ca V 3 regulates cell proliferation and Ca 2+ dynamics in colorectal cancer cells. Understanding this blocking mechanism maybe improve cancer therapies.","journal":"British Journal of Pharmacology","year":2024,"id":456275,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9662,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":894895,"name":"Oumnia Benouna","orcid":"0000-0003-1530-6953","position":1,"is_corresponding":false},{"id":792226,"name":"Roxane Lemoine","orcid":"0000-0002-9889-3614","position":2,"is_corresponding":false},{"id":418052,"name":"Margarita Jacaranda Rosendo‐Pineda","orcid":"0000-0002-4955-8289","position":3,"is_corresponding":false},{"id":1280695,"name":"Tonantzin Guadalupe Anguheven‐Ledezma","orcid":"0009-0005-8029-6167","position":4,"is_corresponding":false},{"id":1281166,"name":"Lizeth Sandoval‐Vazquez","orcid":null,"position":5,"is_corresponding":false},{"id":1281167,"name":"Martin Leonardo Gallegos‐Gomez","orcid":null,"position":6,"is_corresponding":false},{"id":423108,"name":"Leticia Robles-Martínez","orcid":null,"position":7,"is_corresponding":false},{"id":1281168,"name":"Zazil Herrera‐Carrillo","orcid":null,"position":8,"is_corresponding":false},{"id":1280696,"name":"Miguel Ramírez‐Aragón","orcid":"0000-0002-2859-1565","position":9,"is_corresponding":false},{"id":1280697,"name":"Ana Alfaro","orcid":"0000-0001-9620-8399","position":10,"is_corresponding":false},{"id":894896,"name":"Stéphanie Chadet","orcid":"0000-0001-7383-8232","position":11,"is_corresponding":false},{"id":1280698,"name":"Fabio Ferro","orcid":"0000-0002-2982-0024","position":12,"is_corresponding":false},{"id":666262,"name":"Pierre Besson","orcid":"0000-0003-1257-8005","position":13,"is_corresponding":false},{"id":1280699,"name":"Lin‐Hua Jiang","orcid":"0000-0001-6398-0411","position":14,"is_corresponding":false},{"id":134876,"name":"Sadanandan E. 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