Licorice (Glycyrrhiza glabra L.)-Derived Phytochemicals Target Multiple Signaling Pathways to Confer Oncopreventive and Oncotherapeutic Effects

Abstract

Cancer is a highly lethal disease, and its incidence has rapidly increased worldwide over the past few decades. Although chemotherapeutics and surgery are widely used in clinical settings, they are often insufficient to provide the cure for cancer patients. Hence, more effective treatment options are highly needed. Although licorice has been used as a medicinal herb since ancient times, the knowledge about molecular mechanisms behind its diverse bioactivities is still rather new. In this review article, different anticancer properties (antiproliferative, antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory effects) of various bioactive constituents of licorice ( Glycyrrhiza glabra L.) are thoroughly described. Multiple licorice constituents have been shown to bind to and inhibit the activities of various cellular targets, including B-cell lymphoma 2, cyclin-dependent kinase 2, phosphatidylinositol 3-kinase, c-Jun N-terminal kinases, mammalian target of rapamycin, nuclear factor-κB, signal transducer and activator of transcription 3, vascular endothelial growth factor, and matrix metalloproteinase-3, resulting in reduced carcinogenesis in several in vitro and in vivo models with no evident toxicity. Emerging evidence is bringing forth licorice as an anticancer agent as well as bottlenecks in its potential clinical application. It is expected that overcoming toxicity-related obstacles by using novel nanotechnological methods might importantly facilitate the use of anticancer properties of licorice-derived phytochemicals in the future. Therefore, anticancer studies with licorice components must be continued. Overall, licorice could be a natural alternative to the present medication for eradicating new emergent illnesses while having just minor side effects.

Phytochemicals as Invaluable Sources of Potent Antimicrobial Agents to Combat Antibiotic Resistance

“…Glycyrrhizic acid is the primary saponin found in Glycyrrhiza glabra L., of the licorice family [22]. Glycyrrhizic acid and its derivatives are endowed with antibacterial, antitumor, antiviral, antibacterial, and anti-inflammatory activities [23].…”

Sweeteners and the Gut Microbiome: Effects on Gastrointestinal Cancers

“…The administration of glycyrrhizin on SW48 colorectal cancer cells induced apoptosis as the levels of regulator proteins such as Bax expression increased and Bcl-2 levels decreased [72]. HT-29 colon cancer cells treated with different concentrations of glycyrrhiza glabra L. reported the induction of apoptosis at a concentration of 200 µg/mL [73,74]. Additionally, Wister rats administered 15 mg/kg of glycyrrhizic acid were reported to induce apoptosis, suppress precancerous lesion development, and reduce inflammation [75].…”

“…Stevioside administration to a colon carcinoma cell line (Caco-2) suppressed the expression of inflammatory cytokines IL-6, TNF-a, and NF-κB [84]. Additionally, the administration of glycyrrhizic acid inhibited NF-κB expression, which led to the deactivation of inflammatory mediators in colon cells [74,85]. In Wister rats, the administration of 15 mg/kg of oral glycyrrhizic acid reduced the expression of NF-κB, nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) [76].…”

“…Additionally, the researcher reported that steviol treatment caused G1 arrest in both cell lines [67,68]. Glycyrrhizic acid administration to different gastric cancer cell lines (e.g., MGC-803, BGC-823, SGC-7901) induces cell cycle arrest through the downregulation of G1 phase proteins such as cyclin D1, D2, D3, E1, and E2 [74,77]. In addition, 18β-glycyrrhetinic acid, another metabolite of glycyrrhizin, promoted gastric cancer cell autophagy and induced cell cycle arrest in the G0/G1 phase in a transplanted nude mouse model modulating the miR-328-3p/STAT3 signaling pathway [90].…”

Capsaicin: A chili pepper bioactive phytocompound with a potential role in suppressing cancer development and progression

“…Phytoconstituents in human food with antitumorigenic or antimutagenic effects have been the subject of significant interest and intense research (Arslan et al, 2022;Banerjee et al, 2019;Banerjee et al, 2021a;Banerjee et al, 2021b;Bose et al, 2020;De et al, 2023;Kaiser et al, 2021;Mondal et al, 2020;Mondal et al, 2021;Tuli et al, 2022). Capsaicin, chemically known as trans-8-methyl-N-vanillyl-6-nonenamide, possesses various pharmacological properties, such as antioxidant, anti-inflammatory, antidiabetic (Ferdowsi et al, 2023), analgesic (Arora et al, 2021), antiarthritic (Sarwa et al, 2015), cardioprotective (Vaishnava & Wang, 2003), neuroprotective (Abdel-Salam et al, 2020), and antimicrobial (Goci et al, 2021) activities.…”