Antitumor Effects of Quercetin in Hepatocarcinoma In Vitro and In Vivo Models: A Systematic Review

Abstract

Quercetin is a flavonoid present in fruits, vegetables and plants with antioxidant, anti-inflammatory and anticancer properties. Its beneficial activities have been demonstrated in different human pathologies, including hepatoprotective effects against liver disorders. High mortality and late diagnosis of the primary liver tumor hepatocarcinoma (HCC) makes this cancer an interesting target for the study of quercetin effects. Our aim was to systematically review antitumor activities of quercetin in HCC preclinical studies employing single, encapsulated, combined or derived quercetin forms. Literature search was conducted in PubMed, Scopus and Web of Science (WOS), and 39 studies were finally included. We found that 17 articles evaluated quercetin effects alone, six used encapsulated strategy, 10 combined this flavonoid, two decided to co-encapsulate it and only four studied effects of quercetin derivatives, highlighting that only nine included in vivo models. Results evidence the quercetin antiproliferative and proapoptotic properties against HCC either alone and with the mentioned strategies; nevertheless, few investigations assessed specific activities on different processes related with cancer progression. Overall, further studies including animal models are needed to deeper investigate the precise mechanisms of action of quercetin as antitumor agent, as well as the potential of novel strategies aimed to improve quercetin effects in HCC.

Melatonin as an Antitumor Agent against Liver Cancer: An Updated Systematic Review

“…Carcinogenetic processes often involve oxidative stress, and administration of antioxidant molecules may reduce the damage to cancerous hepatocytes [ 61 , 62 , 63 ]. Melatonin acts as an indirect antioxidant and as a direct free radical scavenger and displays an important role as an immunomodulatory and chronobiotic agent in different tissues, including liver [ 6 , 14 , 64 , 65 ].…”

“…In recent years, there has been an increasing interest on the use of flavonoids as anticancer agents [ 62 ]. In vitro experiments have also demonstrated that 2 and 4 mM melatonin co-administration potentiates the proapoptotic effects of EGCG in HepG2 cells by inhibition of Bcl-2 and COX-2, resulting in an enhanced cytotoxicity against HCC cells [ 56 ].…”

Delivery of Natural Agents by Means of Mesoporous Silica Nanospheres as a Promising Anticancer Strategy

“…Quercetin is an excellent free radical scavenging antioxidant [344] and is considered one of the most effective antioxidants [351]. Consequently, quercetin exhibits promising effects against cancer [339,352] in vitro and in vivo [353][354][355][356][357][358][359][360]. Nevertheless, its potential impacts in clinical applications are drastically limited due to its poor solubility, low bioavailability, and instability [361].…”

Beneficial Actions of Orostachys japonica and Its Compounds against Tumors via MAPK Signaling Pathways

“…Notably, it was reported that a low concentration of quercetin acted as an antioxidant, but high-dose quercetin induced oxidative stress against cancer cells, thus displaying anticancer effects [ 113 ]. Recent reports have shown that quercetin is excellent in combating ovarian cancer [ 114 ] and hepatocarcinoma [ 115 ]. In addition, quercetin inhibited the overgrowth of human gastric cancer cells (in the presence of 53 µM quercetin) [ 116 ], MDA-MB-453 (in the presence of 100 µM quercetin) [ 117 ], and MCF-7 (in the presence of 150 µM quercetin) [ 118 ] via the induction of intrinsic and extrinsic apoptosis pathways and cell cycle arrest.…”