TY - JOUR
T1 - Selenofolate inhibits the proliferation of IGROV1 cancer cells independently from folate receptor alpha
AU - Razaghi, Ali
AU - Zickler, Antje Maria
AU - Spallholz, Julian
AU - Kirsch, Gilbert
AU - Björnstedt, Mikael
N1 - Funding Information:
This study was supported by Cancerfonden ( 180429 ), Cancer- och Allergifonden ( 206 ), Radiumhemmets Forskningsfonder ( 171023 ) and Karolinska Institutet .
Publisher Copyright:
© 2021 The Authors
PY - 2021/6
Y1 - 2021/6
N2 - Cancer is one of the main causes of human mortality worldwide and novel chemotherapeutics are required due to the limitations of conventional cancer therapies. For example, using redox selenium compounds as novel chemotherapeutics seem to be very promising. The objective of this study was to explore if folate could be used as a carrier to deliver a newly synthesised selenium derivative selenofolate into cancer cells. Particularly, the cytotoxic effects of this selenofolate compound were investigated in a variety of cancer cell types including lung, liver, and cervical cancers and specifically IGROV1 cells. Our results showed that selenofolate inhibits the growth of cancer cells in-vitro. However, despite the expectations, folate receptor alpha (FRα) was not involved in the transportation of selenofolate compound into the cells i.e. growth inhibition was independent of FRα, suggesting that multiple transporters (e.g. reduced folate carrier-1) are possibly involved in the delivery and internalisation of folate in IGROV1 cells. Additionally, selenofolate did not exert cell death through apoptosis. Instead, anti-proliferative activity showed to be the main cause of growth inhibition of selenolofate in the IGROV1 cell line. In conclusion, selenofolate inhibits the growth of cancer cells and thus, may be explored further as a potential chemotherapeutic agent.
AB - Cancer is one of the main causes of human mortality worldwide and novel chemotherapeutics are required due to the limitations of conventional cancer therapies. For example, using redox selenium compounds as novel chemotherapeutics seem to be very promising. The objective of this study was to explore if folate could be used as a carrier to deliver a newly synthesised selenium derivative selenofolate into cancer cells. Particularly, the cytotoxic effects of this selenofolate compound were investigated in a variety of cancer cell types including lung, liver, and cervical cancers and specifically IGROV1 cells. Our results showed that selenofolate inhibits the growth of cancer cells in-vitro. However, despite the expectations, folate receptor alpha (FRα) was not involved in the transportation of selenofolate compound into the cells i.e. growth inhibition was independent of FRα, suggesting that multiple transporters (e.g. reduced folate carrier-1) are possibly involved in the delivery and internalisation of folate in IGROV1 cells. Additionally, selenofolate did not exert cell death through apoptosis. Instead, anti-proliferative activity showed to be the main cause of growth inhibition of selenolofate in the IGROV1 cell line. In conclusion, selenofolate inhibits the growth of cancer cells and thus, may be explored further as a potential chemotherapeutic agent.
KW - Cancer
KW - Folate
KW - Folate receptor
KW - Selenofolate
KW - Selenotherapy
UR - http://www.scopus.com/inward/record.url?scp=85107743571&partnerID=8YFLogxK
U2 - 10.1016/j.heliyon.2021.e07254
DO - 10.1016/j.heliyon.2021.e07254
M3 - Article
AN - SCOPUS:85107743571
VL - 7
JO - Heliyon
JF - Heliyon
SN - 2405-8440
IS - 6
M1 - e07254
ER -