Electronic Resource
Phenothiazines alter plasma membrane properties and sensitize cancer cells to injury by inhibiting annexin-mediated repair
| العنوان: | Phenothiazines alter plasma membrane properties and sensitize cancer cells to injury by inhibiting annexin-mediated repair |
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| المؤلفون: | Heitmann, Anne Sofie Busk, Zanjani, Ali Asghar Hakami, Klenow, Martin Berg, Mularski, Anna, Sønder, Stine Lauritzen, Lund, Frederik Wendelboe, Boye, Theresa Louise, Dias, Catarina, Bendix, Poul Martin, Simonsen, Adam Cohen, Khandelia, Himanshu, Nylandsted, Jesper |
| المصدر: | Heitmann , A S B , Zanjani , A A H , Klenow , M B , Mularski , A , Sønder , S L , Lund , F W , Boye , T L , Dias , C , Bendix , P M , Simonsen , A C , Khandelia , H & Nylandsted , J 2021 , ' Phenothiazines alter plasma membrane properties and sensitize cancer cells to injury by inhibiting annexin-mediated repair ' , Journal of Biological Chemistry , vol. 297 , no. 2 , 101012 . |
| بيانات النشر: | 2021 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Repair of damaged plasma membrane in eukaryotic cells is largely dependent on the binding of annexin repair proteins to phospholipids. Changing the biophysical properties of the plasma membrane may provide means to compromise annexin-mediated repair and sensitize cells to injury. Since, cancer cells experience heightened membrane stress and are more dependent on efficient plasma membrane repair, inhibiting repair may provide approaches to sensitize cancer cells to plasma membrane damage and cell death. Here, we show that derivatives of phenothiazines, which have widespread use in the fields of psychiatry and allergy treatment, strongly sensitize cancer cells to mechanical-, chemical-, and heat-induced injury by inhibiting annexin-mediated plasma membrane repair. Using a combination of cell biology, biophysics, and computer simulations, we show that trifluoperazine acts by thinning the membrane bilayer, making it more fragile and prone to ruptures. Secondly, it decreases annexin binding by compromising the lateral diffusion of phosphatidylserine, inhibiting the ability of annexins to curve and shape membranes, which is essential for their function in plasma membrane repair. Our results reveal a novel avenue to target cancer cells by compromising plasma membrane repair in combination with noninvasive approaches that induce membrane injuries. |
| مصطلحات الفهرس: | article |
| URL: | |
| الاتاحة: | Open access content. Open access content info:eu-repo/semantics/openAccess |
| ملاحظة: | application/pdf English |
| Other Numbers: | DAV oai:pure.atira.dk:publications/74314f8e-d503-4739-8f09-6e49f36d3f9f 1322765415 |
| المصدر المساهم: | UNIV OF COPENHAGEN From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1322765415 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |