Effects of the Licorice Extract against Tumor Growth and Cisplatin-Induced Toxicity in a Mouse Xenograft Model of Colon Cancer

Abstract

Cisplatin (cis-diamminedichloroplatinum II) is a platinum coordinated complex that is widely used as an antineoplastic agent for the treatment of many solid tumors, including cancers of the ovary, testis, lung, bladder, head and neck, cervix and endometrium.1) Despite its excellent anticancer activity, the clinical use of cisplatin is often limited by its undesirable side effects, such as severe nephrotoxicity and hepatotoxicity. 2,3) Although the precise mechanism for this cisplatin-induced toxicity is not well understood, cisplatin is taken up preferentially and accumulates in the human liver and kidney cells, 4) resulting in the enhanced production of reactive oxygen species (ROS) and the decrease in the antioxidant enzymes.5,6) Therefore, antioxidants have been administered before a cisplatin treatment to protect against nephrotoxicity. 7)Licorice is an esteemed crude drug in both the Orient and Occident that is originated from the dried roots of several Glycyrrhiza species, including Glycyrrhiza uralensis FISCHER, G. glabra LINNE and G. inflata BATALIN. 8,9) In Chinese traditional medicine, licorice remains one of the most commonly prescribed herbs and has been used in the treatment of various ailments ranging from tuberculosis to peptic ulcers.10) Licorice has also been employed as a flavoring and sweetening agent, as well as a demulcent and expectorant in Western countries.11) The chemical constituents of licorice include glycyrrhizin and its aglycone, glycyrrhetinic acid, which are originally isolated from aqueous extracts and are used in the treatment of hyperlipemia, atherosclerosis, viral diseases, allergic inflammation and hepatotoxicity.12,13) The acetone or ethanol extract of licorice has species-specific flavonoids, such as liquiritin, isoliquiritin and their corresponding aglycones, glabridin, glabrol, glabrene, hispaglabridin A and hispaglabridin B.14,15) These flavonoids exhibit antioxidative, 16) superoxide scavenging 16) and anticarcinogenic activities.17) However, in vivo antitumor activity of a licorice extract and its protective activity on cisplatin-induced toxicity have not yet been studied.In the present study to assess the antitumor activity of a licorice extract and whether it has the potential to serve as a beneficial supplement during cisplatin chemotherapy, we examined the inhibitory effect of the licorice extract alone and in combination with cisplatin on the tumor growth, and its protective effect against cisplatin-induced nephrotoxicity and hepatotoxicity in mice xenografted with mouse colon carcinoma cells. MATERIALS AND METHODSChemical Cisplatin, phenylmethylsulfonyl fluoride (PMSF), sodium nitrite, 1,1,3,3-tetramethoxypropane, reduced glutathione (GSH), 5,5Ј-dithiobis(2-nitrobenzoic acid) (DTNB), glutathione reductase, reduced nicotinamide adenine dinucleotide phosphate (NADPH), superoxide dismutase (SOD), xanthine oxidase, a-naphthylamine, sulfanilic acid, xanthine, catalase and 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (purpald ® ) were purchased from SigmaAldrich Chem...

Licochalcone-E induces caspase-dependent death of human pharyngeal squamous carcinoma cells through the extrinsic and intrinsic apoptotic signaling pathways

“…Previous studies on the development of chemotherapeutic agents have been focused on inducing cancer-specific cell death through the modulation of apoptosis, or programmed cell death. Furthermore, to overcome the side effects of current chemotherapeutic agents, studies have focused on the anti-cancer activity of natural compounds purified from herbal plants (7,(11)(12)(13)(14)(15). As a result of these studies, the US Food and Drug Administration approved the clinical use of a medicinal herbal plant-derived natural compound with anti-cancer activity for cancer therapy (16).…”

“…Licorice has been used as a medication for stomach ulcers, bronchitis and sore throats (7,17). Furthermore, the anticancer activity of licorice has been reported in breast (18,19), oral (11), colon (12) and prostate cancer (13). Licorice inhibits metastasis (18), has anti-proliferative properties (19), increases apoptosis and may cause cell cycle arrest (14).…”

Anti-tumor effect of licochalcone-E is mediated by caspase-dependent apoptosis through extrinsic and intrinsic apoptotic signaling pathways in KB cancer cells

“…Recent studies have reported that licorice roots contain multiple bioactive components such as saponins, flavonoids, and coumarins [13][14][15]. Furthermore, licorice has been shown to have anticancer effects in various types of cancer such as colon [16], lung [17,18], breast [19,20], prostate [21], and oral cancers [11] through metastatic inhibition [19], anti-proliferative properties [20], increased apoptosis [11,22], and cell cycle arrest [23].…”

Endothelium-independent vasodilation induced by kolaviron, a biflavonoid complex from Garcinia kola seeds, in rat superior mesenteric arteries

“…Recently there has been an upsurge of interest in the therapeutic potentials of medicinal plants as antioxidants in alleviating oxidative stress-induced pathologies (Lans et al, 2007;Lee et al, 2007). Several studies revealed that medicinal plants contain diverse classes of bioactive compounds such as polyphenols, tocopherols, alkaloids, etc.…”

“…Several studies revealed that medicinal plants contain diverse classes of bioactive compounds such as polyphenols, tocopherols, alkaloids, etc. (Gordana et al, 2004;Lee et al, 2007). Among them, flavonoids are particularly attractive as they are known to exhibit various pharmacological properties such as vasoprotection, anti-carcinogenic, anti-microbial, antiinflammatory and anti-proliferative effects (Gordana et al, 2004).…”