Leaf and Root Extracts from Campomanesia adamantium (Myrtaceae) Promote Apoptotic Death of Leukemic Cells via Activation of Intracellular Calcium and Caspase-3

Abstract

Phytochemical studies are seeking new alternatives to prevent or treat cancer, including different types of leukemias. Campomanesia adamantium, commonly known as guavira or guabiroba, exhibits pharmacological properties including antioxidant, antimicrobial, and antiproliferative activities. Considering the anticancer potential of this plant species, the aim of this study was to evaluate the antileukemic activity and the chemical composition of aqueous extracts from the leaves (AECL) and roots (AECR) of C. adamantium and their possible mechanisms of action. The extracts were analyzed by LC-DAD-MS, and their constituents were identified based on the UV, MS, and MS/MS data. The AECL and AECR showed different chemical compositions, which were identified as main compounds glycosylated flavonols from AECL and ellagic acid and their derivatives from AECR. The cytotoxicity promoted by these extracts were evaluated using human peripheral blood mononuclear cells and Jurkat leukemic cell line. The cell death profile was evaluated using annexin-V-FITC and propidium iodide labeling. Changes in the mitochondrial membrane potential, the activity of caspases, and intracellular calcium levels were assessed. The cell cycle profile was evaluated using propidium iodide. Both extracts caused concentration-dependent cytotoxicity only in Jurkat cells via late apoptosis. This activity was associated with loss of the mitochondrial membrane potential, activation of caspases-9 and -3, changes in intracellular calcium levels, and cell cycle arrest in S-phase. Therefore, the antileukemic activity of the AECL and AECR is mediated by mitochondrial dysfunction and intracellular messengers, which activate the intrinsic apoptotic pathway. Hence, aqueous extracts of the leaves and roots of C. adamantium show therapeutic potential for use in the prevention and treatment of diseases associated the proliferation of tumor cell.

Effect of Polyphenols From Campomanesia adamantium on Platelet Aggregation and Inhibition of Cyclooxygenases: Molecular Docking and in Vitro Analysis

“…In the study performed by de Souza et al (2017) on the extract ethanol:water (70:30) of the C. adamantium peel, evaluating anti-inflammatory activity and its chemical composition, the study presented flavonoids and chalcones as the extract main constituents, similar to found in our study. Furthermore, several phytoconstituents from different parts of this plant have been reported, such as quercetin, myricetin, myricitrin, gallic acid, ellagic acid, condensed tannins, among others ( Ferreira et al, 2013 ; Campos et al, 2017 ; Viscardi et al, 2017 ). The presence of quercetin and myricetin in the extract of C. adamantium leaves has also been reported as the cause of their anti-inflammatory action ( Ferreira et al, 2013 ).…”

Embryogenic potential of the callus of gabirobeira, Campomanesia adamantium (Cambess) O. Berg

“…Its fruit can be consumed in natura or in the form of juice, ice cream, popsicles, candy, or liqueur (Bardiviesso, Maruyama, Reis, Modesto, & Rezende, 2011). In addition, studies have demonstrated the species to have medicinal properties including anti-inflammatory, antihyperalgesic and antidepressant actions (Souza et al, 2014), antimicrobial (Sá et al, 2018), as well as antidiarrheal (Lescano et al, 2016) and antileukemic activity, thus demonstrating therapeutic potential for diseases associated with the proliferation of tumor cells (Campos et al, 2017).…”

Therapeutic Potential of Brazilian Cerrado Campomanesia Species on Metabolic Dysfunctions

“…Moreover, this plant has been used in the traditional medicine since previous studies have shown beneficial effects on health from C. adamantium fruits, such as antimicrobial [ 75 , 76 ], antidepressant, antihyperalgesic, and anti-inflammatory effects [ 77 ], antidiarrheal activity [ 78 ], and antiproliferative action [ 38 , 79 ]. In addition to these effects, other studies described that leaves and roots have exhibited antiproliferative action against prostate cancer cells [ 38 ] and, more recently, promoted apoptotic death of leukemic cells [ 39 ]. It is also said to demonstrate anti-inflammatory and antinociceptive effects [ 31 ], antioxidant effects [ 33 , 34 , 35 , 36 , 79 ], and antimicrobial activity [ 80 ].…”

“…Among other species used with medicinal purposes are the genus Campomanesia , belonging to the family Myrtaceae, which is popularly known as guavira [ 21 ]. It has demonstrated effects on health, such as antiulcerogenic [ 29 ], antiprotozoal [ 30 ], anti-inflammatory [ 31 , 32 ], antioxidant [ 33 , 34 , 35 , 36 , 37 ], and antiproliferative [ 38 , 39 ] activities.…”