Abstract
Nowadays, one of medicine’s main and most challenging aims is finding effective ways to treat cancer. Unfortunately, although there are numerous anti-cancerous drugs, such as cisplatin, more and more cancerous cells create drug resistance. Thus, it is equally important to find new medicines and research the drug resistance phenomenon and possibilities to avoid this mechanism. Ion channels, including chloride channels, play an important role in the drug resistance phenomenon. Our article focuses on the chloride channels, especially the volume-regulated channels (VRAC) and CLC chloride channels family. VRAC induces multidrug resistance (MDR) by causing apoptosis connected with apoptotic volume decrease (AVD) and VRAC are responsible for the transport of anti-cancerous drugs such as cisplatin. VRACs are a group of heterogenic complexes made from leucine-rich repetition with 8A (LRRC8A) and a subunit LRRC8B-E responsible for the properties. There are probably other subunits, which can create those channels, for example, TTYH1 and TTYH2. It is also known that the ClC family is involved in creating MDR in mainly two mechanisms—by changing the cell metabolism or acidification of the cell. The most researched chloride channel from this family is the CLC-3 channel. However, other channels are playing an important role in inducing MDR as well. In this paper, we review the role of chloride channels in MDR and establish the role of the channels in the MDR phenomenon.
Highlights
The clinical effects of cytostatic drugs are weakened by drug resistance in some cancer cells
Channels play an essential role in the multidrug resistance phenomenon, especially the ClC family and volume-regulated channels (VRAC)/volume sensitive outward righting channel (VSOR)
VRAC/VSOR channels are important cellular elements associated with the proliferation, migration, and multidrug resistance of cancer cells
Summary
Cancer cases have significantly increased over the last decade. The mainstay of treating these diseases is a surgical procedure, followed by radiotherapy and chemotherapy involving cytostatic drugs [1]. They allow the flow of inorganic ions and larger organic osmolytes from and into the cell, which causes an osmotic flow of water [14] These include numerous anionic and cationic channels, such as the volume regulated anion channel (VRAC), known for its low outward straightening currents by the volume sensitive outward righting channel (VSOR). This channel is activated in response to an increase in the cell volume and conditions the outflow of chlorides and organic osmolytes from the cell, leading to a regulatory volume decrease (RVD) [14–18]. D), which is associated with the occurrence of apoptosis in many types of tumor cells [43,47,48]
Sign-in/Register to view highlights & summary 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.
