NDLI: Esculetin, a natural coumarin compound, evokes $Ca^{2+}$ movement and activation of $Ca^{2+}-associated$ mitochondrial apoptotic pathways that involved cell cycle arrest in ZR-75-1 human breast cancer cells

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chang, Hong-Tai Chou, Chiang-Ting Lin, You-Sheng Shieh, Pochuen Kuo, Daih-Huang Jan, Chung-Ren Liang, Wei-Zhe
Description	Country affiliation: China Author Affiliation: Chang HT ( Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan, Republic of China.); Chou CT ( Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia-Yi, 613, Taiwan.); Lin YS ( Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi, 613, Taiwan.); Shieh P ( Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan.); Kuo DH ( Department of Pharmacy, Tajen University, Pingtung, 907, Taiwan.); Jan CR ( Department of Pharmacy, Tajen University, Pingtung, 907, Taiwan.); Liang WZ ( Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan.)
Abstract	Esculetin (6,7-dihydroxycoumarin), a derivative of coumarin compound, is found in traditional medicinal herbs. It has been shown that esculetin triggers diverse cellular signal transduction pathways leading to regulation of physiology in different models. However, whether esculetin affects $Ca^{2+}$ homeostasis in breast cancer cells has not been explored. This study examined the underlying mechanism of cytotoxicity induced by esculetin and established the relationship between $Ca^{2+}$ signaling and cytotoxicity in human breast cancer cells. The results showed that esculetin induced concentration-dependent rises in the intracellular $Ca^{2+}$ concentration $([Ca^{2+}]_{i})$ in ZR-75-1 (but not in MCF-7 and MDA-MB-231) human breast cancer cells. In ZR-75-1 cells, this $Ca^{2+}$ signal response was reduced by removing extracellular $Ca^{2+}$ and was inhibited by the store-operated $Ca^{2+}$ channel blocker 2-aminoethoxydiphenyl borate (2-APB). In $Ca^{2+}-free$ medium, pre-treatment with the endoplasmic reticulum $Ca^{2+}$ pump inhibitor thapsigargin (TG) abolished esculetin-induced $[Ca^{2+}]_{i}$ rises. Conversely, incubation with esculetin abolished TG-induced $[Ca^{2+}]_{i}$ rises. Esculetin induced cytotoxicity that involved apoptosis, as supported by the reduction of mitochondrial membrane potential and the release of cytochrome c and the proteolytic activation of caspase-9/caspase-3, which were partially reversed by pre-chelating cytosolic $Ca^{2+}$ with 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid-acetoxymethyl ester (BAPTA-AM). Moreover, esculetin increased the percentage of cells in G2/M phase and regulated the expressions of p53, p21, CDK1, and cyclin B1. Together, in ZR-75-1 cells, esculetin induced $[Ca^{2+}]_{i}$ rises by releasing $Ca^{2+}$ from the ER and causing $Ca^{2+}$ influx through 2-APB-sensitive store-operated $Ca^{2+}$ entry. Furthermore, esculetin activated $Ca^{2+}-associated$ mitochondrial apoptotic pathways that involved G2/M cell cycle arrest.
File Format	HTM / HTML
ISSN	10104283
Issue Number	4
Journal	Tumor Biology
Volume Number	37
e-ISSN	14230380
Language	English
Publisher	Springer
Publisher Date	2016-04-01
Publisher Place	Netherlands
Access Restriction	Subscribed
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in