Abstract
Baicalein (5,6,7-trihydroxyflavone) (1) has been found to be active against a wide variety of cancer cells. However, the molecular mechanism underlying the effects of 1 on the induction of Ca(2+) movement and cytotoxicity in human breast cancer cells is unknown. This study examined the relationship between 1-induced Ca(2+) signaling and cytotoxicity in ZR-75-1 human breast cancer cells. The in vitro investigations reported herein produced the following results: (i) Compound 1 increased intracellular Ca(2+) concentration ([Ca(2+)]i) in a concentration-dependent manner. The signal was decreased by approximately 50% by removal of extracellular Ca(2+). (ii) Compound 1-triggered [Ca(2+)]i increases were significantly suppressed by store-operated Ca(2+) channel blockers 2-aminoethoxydiphenyl borate (2-APB) and the PKC inhibitor GF109203X. (iii) In Ca(2+)-free medium, compound 1-induced [Ca(2+)]i increases were also inhibited by GF109203X. Furthermore, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) or 2,5-ditert-butylhydroquinone (BHQ) abolished 1-induced [Ca(2+)]i increases. Inhibition of phospholipase C (PLC) with U73122 abolished 1-induced [Ca(2+)]i increases. (iv) Compound 1 (20-40 μM) caused cytotoxicity, increased reactive oxygen species (ROS) production, and activated caspase-9/caspase-3. Furthermore, compound 1-induced apoptosis was significantly inhibited by prechelating cytosolic Ca(2+) with BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester) or by decreasing ROS with the antioxidant NAC (N-acetylcysteine). Together, baicalein (1) induced a [Ca(2+)]i increase by inducing PLC-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via PKC-dependent, 2-APB-sensitive store-operated Ca(2+) channels. Moreover, baicalein (1) induced Ca(2+)-associated apoptosis involved ROS production in ZR-75-1 cells.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
