TY - JOUR
T1 - Effects of Sorafenib and Quercetin Alone or in Combination in Treating Hepatocellular Carcinoma
T2 - In Vitro and In Vivo Approaches
AU - Abdu, Suzan
AU - Juaid, Nouf
AU - Amin, Amr
AU - Moulay, Mohamed
AU - Miled, Nabil
N1 - Funding Information:
This research was funded by University of Jeddah (# UJ-21-ICI-10).
Publisher Copyright:
© 2022 by the authors.
PY - 2022/11
Y1 - 2022/11
N2 - Sorafenib is the first drug approved to treat advanced hepatocellular carcinoma (HCC) and continues as the gold-standard therapy against HCC. However, acquired drug resistance represents a main concern about sorafenib therapy. The flavanol quercetin found in plants has shown great anti-cancer and anti-inflammatory properties. In this work, quercetin was used as a therapeutic agent alone or in combination with a sorafenib chemotherapy drug to improve the routine HCC treatment with sorafenib. The in vitro and in vivo results presented here confirm that quercetin alone or in combination with sorafenib significantly inhibited HCC growth, induced cell cycle arrest and induced apoptosis and necrosis. Further molecular data shown in this report demonstrate that quercetin alone or combined with sorafenib downregulated key inflammatory, proliferative and angiogenesis-related genes (TNF-α, VEGF, P53 and NF-κB). Combined quercetin/sorafenib treatment markedly improved the morphology of the induced liver damage and showed significant antioxidant and anti-tumor effects. The advantage of combined treatment efficacy reported here can be attributed to quercetin’s prominent effects in modulating cell cycle arrest, apoptosis, oxidative stress and inflammation.
AB - Sorafenib is the first drug approved to treat advanced hepatocellular carcinoma (HCC) and continues as the gold-standard therapy against HCC. However, acquired drug resistance represents a main concern about sorafenib therapy. The flavanol quercetin found in plants has shown great anti-cancer and anti-inflammatory properties. In this work, quercetin was used as a therapeutic agent alone or in combination with a sorafenib chemotherapy drug to improve the routine HCC treatment with sorafenib. The in vitro and in vivo results presented here confirm that quercetin alone or in combination with sorafenib significantly inhibited HCC growth, induced cell cycle arrest and induced apoptosis and necrosis. Further molecular data shown in this report demonstrate that quercetin alone or combined with sorafenib downregulated key inflammatory, proliferative and angiogenesis-related genes (TNF-α, VEGF, P53 and NF-κB). Combined quercetin/sorafenib treatment markedly improved the morphology of the induced liver damage and showed significant antioxidant and anti-tumor effects. The advantage of combined treatment efficacy reported here can be attributed to quercetin’s prominent effects in modulating cell cycle arrest, apoptosis, oxidative stress and inflammation.
KW - HCC
KW - inflammation
KW - necrosis
KW - quercetin
KW - sorafenib
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U2 - 10.3390/molecules27228082
DO - 10.3390/molecules27228082
M3 - Article
C2 - 36432184
AN - SCOPUS:85142652401
SN - 1420-3049
VL - 27
JO - Molecules
JF - Molecules
IS - 22
M1 - 8082
ER -