Vitexicarpin suppresses colorectal and non-small cell lung cancer via selective inhibition of Anoctamin 1

Colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) remain among the most challenging malignancies to treat due to therapy complexity, adverse events, and dose-limiting toxicities, which often result in treatment failure. NSCLC, in particular, has a high mortality rate attributed to late-...

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Main Authors: Yohan Seo, Sion Lee, Raju Das, Sung Baek Jeong, Chul Soon Park, Minuk Kim, Deok Kyu Yoon, Armin Sultana, Kantu Das, Jae-Eon Lee, Yong Hyun Jeon, Phan Thi Thanh Huong, Nguyen Xuan Nhiem, Joohan Woo
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1557193/full
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author Yohan Seo
Yohan Seo
Sion Lee
Raju Das
Sung Baek Jeong
Chul Soon Park
Minuk Kim
Deok Kyu Yoon
Armin Sultana
Kantu Das
Jae-Eon Lee
Yong Hyun Jeon
Phan Thi Thanh Huong
Nguyen Xuan Nhiem
Joohan Woo
Joohan Woo
author_facet Yohan Seo
Yohan Seo
Sion Lee
Raju Das
Sung Baek Jeong
Chul Soon Park
Minuk Kim
Deok Kyu Yoon
Armin Sultana
Kantu Das
Jae-Eon Lee
Yong Hyun Jeon
Phan Thi Thanh Huong
Nguyen Xuan Nhiem
Joohan Woo
Joohan Woo
author_sort Yohan Seo
collection DOAJ
description Colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) remain among the most challenging malignancies to treat due to therapy complexity, adverse events, and dose-limiting toxicities, which often result in treatment failure. NSCLC, in particular, has a high mortality rate attributed to late-stage diagnosis and therapeutic resistance. Anoctamin 1 (ANO1), a calcium-activated chloride channel, has been implicated in cancer progression and is an emerging therapeutic target. In this study, we identified vitexicarpin, a flavonoid isolated from Vitex trifolia, as a novel ANO1 inhibitor with anticancer potential. Vitexicarpin inhibited ANO1 channel function, reduced ANO1 protein levels, decreased cancer cell viability, and induced apoptosis in CRC and NSCLC cell lines. Importantly, vitexicarpin exhibited minimal hepatotoxicity and negligible hERG channel inhibition, supporting its safety profile. Collectively, our findings suggest that vitexicarpin is a promising candidate for the treatment of CRC and NSCLC through selective inhibition of ANO1.
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institution OA Journals
issn 1663-9812
language English
publishDate 2025-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Pharmacology
spelling doaj-art-078f7f2831ec446cbbb940683e8362682025-08-20T02:34:32ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15571931557193Vitexicarpin suppresses colorectal and non-small cell lung cancer via selective inhibition of Anoctamin 1Yohan Seo0Yohan Seo1Sion Lee2Raju Das3Sung Baek Jeong4Chul Soon Park5Minuk Kim6Deok Kyu Yoon7Armin Sultana8Kantu Das9Jae-Eon Lee10Yong Hyun Jeon11Phan Thi Thanh Huong12Nguyen Xuan Nhiem13Joohan Woo14Joohan Woo15Department of Bio-nanomaterials, Bio Campus of Korea Polytechnics, Nonsan, Republic of KoreaNew Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (KMEDIhub), Daegu, Republic of KoreaNew Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (KMEDIhub), Daegu, Republic of KoreaDepartment of Physiology, Dongguk University College of Medicine, Gyeongju, Republic of KoreaNew Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (KMEDIhub), Daegu, Republic of KoreaDepartment of Bio-nanomaterials, Bio Campus of Korea Polytechnics, Nonsan, Republic of KoreaDepartment of Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (KMEDI hub), Daegu, Republic of KoreaDepartment of Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (KMEDI hub), Daegu, Republic of KoreaDepartment of Physiology, Dongguk University College of Medicine, Gyeongju, Republic of KoreaDepartment of Computer Science, Southern University Bangladesh, Chittagong, BangladeshPreclincial Research Center (PRC), Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI hub), Daegu, Republic of KoreaPreclincial Research Center (PRC), Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI hub), Daegu, Republic of KoreaInstitute of Marine and Biochemistry, Vietnam Academy of Science and Technology (VAST), Hanoi, VietnamInstitute of Marine and Biochemistry, Vietnam Academy of Science and Technology (VAST), Hanoi, VietnamDepartment of Physiology, Dongguk University College of Medicine, Gyeongju, Republic of KoreaChannelopathy Research Center (CRC), Dongguk University College of Medicine, Goyang, Gyeonggi-do, Republic of KoreaColorectal cancer (CRC) and non-small cell lung cancer (NSCLC) remain among the most challenging malignancies to treat due to therapy complexity, adverse events, and dose-limiting toxicities, which often result in treatment failure. NSCLC, in particular, has a high mortality rate attributed to late-stage diagnosis and therapeutic resistance. Anoctamin 1 (ANO1), a calcium-activated chloride channel, has been implicated in cancer progression and is an emerging therapeutic target. In this study, we identified vitexicarpin, a flavonoid isolated from Vitex trifolia, as a novel ANO1 inhibitor with anticancer potential. Vitexicarpin inhibited ANO1 channel function, reduced ANO1 protein levels, decreased cancer cell viability, and induced apoptosis in CRC and NSCLC cell lines. Importantly, vitexicarpin exhibited minimal hepatotoxicity and negligible hERG channel inhibition, supporting its safety profile. Collectively, our findings suggest that vitexicarpin is a promising candidate for the treatment of CRC and NSCLC through selective inhibition of ANO1.https://www.frontiersin.org/articles/10.3389/fphar.2025.1557193/fullANO1vitexicarpincolorectal cancernon-small cell lung cancerapoptosis
spellingShingle Yohan Seo
Yohan Seo
Sion Lee
Raju Das
Sung Baek Jeong
Chul Soon Park
Minuk Kim
Deok Kyu Yoon
Armin Sultana
Kantu Das
Jae-Eon Lee
Yong Hyun Jeon
Phan Thi Thanh Huong
Nguyen Xuan Nhiem
Joohan Woo
Joohan Woo
Vitexicarpin suppresses colorectal and non-small cell lung cancer via selective inhibition of Anoctamin 1
Frontiers in Pharmacology
ANO1
vitexicarpin
colorectal cancer
non-small cell lung cancer
apoptosis
title Vitexicarpin suppresses colorectal and non-small cell lung cancer via selective inhibition of Anoctamin 1
title_full Vitexicarpin suppresses colorectal and non-small cell lung cancer via selective inhibition of Anoctamin 1
title_fullStr Vitexicarpin suppresses colorectal and non-small cell lung cancer via selective inhibition of Anoctamin 1
title_full_unstemmed Vitexicarpin suppresses colorectal and non-small cell lung cancer via selective inhibition of Anoctamin 1
title_short Vitexicarpin suppresses colorectal and non-small cell lung cancer via selective inhibition of Anoctamin 1
title_sort vitexicarpin suppresses colorectal and non small cell lung cancer via selective inhibition of anoctamin 1
topic ANO1
vitexicarpin
colorectal cancer
non-small cell lung cancer
apoptosis
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1557193/full
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