TY - JOUR
T1 - Investigating potential anti-proliferative activity of different statins against five cancer cell lines
AU - Sarbassova, Gauhar
AU - Nurlan, Nurbek
AU - Raddam Al shammari, Basim
AU - Francis, Nidhish
AU - Alshammari, Mohammed
AU - Aljofan, Mohamad
N1 - Funding Information:
This work is partly funded by the Social Policy Grant awarded to M.A. by the School of Medicine at Nazarbayev University. The authors would also like to thank the School of Medicine- Nazarbayev University for providing some of the materials needed for this work.
Publisher Copyright:
© 2023
© 2023 The Authors. Published by Elsevier B.V. on behalf of King Saud University.
PY - 2023/5
Y1 - 2023/5
N2 - Statins have been reported to have potential anti-proliferative effects through an unknown mechanism. This study aims to investigate the anti-proliferative activities of five statins, including simvastatin, rosuvastatin, fluvastatin, atorvastatin, and pravastatin, against five different cancer cell lines; cervical epithelial carcinoma DoTc2 4510, malignant melanoma A-375, muscle Ewing's sarcoma A-673, hepatocellular carcinoma HUH-7, as well as breast cancer cells MCF-7. At 100 µM, simvastatin and atorvastatin significantly inhibited 70% of cellular proliferation. At the same concentration, rosuvastatin and fluvastatin showed about 50% of inhibition only in A-375 and A-673 cancer cells in a time- and dose-dependent manner. Of all the statin drugs used, pravastatin had the least inhibitory effect on all the cancer cell lines. Western Blot analysis showed a decrease in mTOR level, and the expression of p53 tumour suppression and BCL-2 proteins was relatively elevated compared to the untreated cells. Simvastatin and atorvastatin may inhibit cellular proliferation via BCL-2/p53, Bax/Bak, and PI3K/Akt/mTOR signalling pathways. This is the first research to evaluate the anti-cancer effects of simvastatin, rosuvastatin, fluvastatin, atorvastatin, and pravastatin against five different cell lines from distinct origins and provided a relevant comparison of their efficacies for their anti-proliferative activity.
AB - Statins have been reported to have potential anti-proliferative effects through an unknown mechanism. This study aims to investigate the anti-proliferative activities of five statins, including simvastatin, rosuvastatin, fluvastatin, atorvastatin, and pravastatin, against five different cancer cell lines; cervical epithelial carcinoma DoTc2 4510, malignant melanoma A-375, muscle Ewing's sarcoma A-673, hepatocellular carcinoma HUH-7, as well as breast cancer cells MCF-7. At 100 µM, simvastatin and atorvastatin significantly inhibited 70% of cellular proliferation. At the same concentration, rosuvastatin and fluvastatin showed about 50% of inhibition only in A-375 and A-673 cancer cells in a time- and dose-dependent manner. Of all the statin drugs used, pravastatin had the least inhibitory effect on all the cancer cell lines. Western Blot analysis showed a decrease in mTOR level, and the expression of p53 tumour suppression and BCL-2 proteins was relatively elevated compared to the untreated cells. Simvastatin and atorvastatin may inhibit cellular proliferation via BCL-2/p53, Bax/Bak, and PI3K/Akt/mTOR signalling pathways. This is the first research to evaluate the anti-cancer effects of simvastatin, rosuvastatin, fluvastatin, atorvastatin, and pravastatin against five different cell lines from distinct origins and provided a relevant comparison of their efficacies for their anti-proliferative activity.
KW - Cancer
KW - Cell signalling
KW - mTOR
KW - P53
KW - Proliferation
KW - Statins
UR - http://www.scopus.com/inward/record.url?scp=85151297611&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85151297611&partnerID=8YFLogxK
U2 - 10.1016/j.jsps.2023.03.013
DO - 10.1016/j.jsps.2023.03.013
M3 - Article
C2 - 37181137
AN - SCOPUS:85151297611
SN - 1319-0164
VL - 31
SP - 727
EP - 735
JO - Saudi Pharmaceutical Journal
JF - Saudi Pharmaceutical Journal
IS - 5
ER -