Inhibitory Effect of Cuphea aequipetala Extracts on Murine B16F10 Melanoma In Vitro and In Vivo

Abstract

Cuphea aequipetala (C. aequipetala) has been used in Mexican traditional medicine since prehispanic times to treat tumors. In this paper, we evaluated the antiproliferative and apoptotic effect of the methanolic and aqueous extracts of C. aequipetala on several cancer cell lines including the B16F10 cell line of murine melanoma and carried a murine model assay. In vitro assay analyzed the effect in the cellular cycle and several indicators of apoptosis, such as the caspase-3 activity, DNA fragmentation, phosphatidylserine exposure (Annexin-V), and induction of cell membrane permeabilization (propidium iodide) in the B16F10 cells. In vivo, groups of C57BL/6 female mice were subcutaneously injected with 5x105 B16F10 cells and treated with 25 mg/mL of C. aequipetala extracts via oral. Aqueous and methanolic extracts showed a cytotoxic effect in MCF-7, HepG2, and B16F10 cell lines. The methanolic extract showed more antiproliferative effect with less concentration, and for this reason, the in vitro experiments were only continued with it. This extract was able to induce accumulation of cells on G1 phase of the cell cycle; moreover, it was able to induce DNA fragmentation and increase the activity of caspase-3 in B16F10 cells. On the other hand, in the murine model of melanoma, the aqueous extract showed a greater reduction of tumor size in comparison with the methanolic extract, showing an 80% reduction versus one of around 31%, both compared with the untreated control, indicating a better antitumor effect of C. aequipetala aqueous extract via oral administration. In conclusion, the in vitro data showed that both C. aequipetala extracts were able to induce cytotoxicity through the apoptosis pathway in B16F10 cells, and in vivo, the oral administration of aqueous extract reduces the melanoma tumoral mass, suggesting an important antitumoral effect and the perspective to search for effector molecules involved in it.

Macromolecular Structure of Linearly Arranged Eukaryotic Chromosomes

“…Alcohols: methanol showed a cytotoxic and antiproliferative effect in MCF-7, HepG2 and B16F10 cell lines [ 61 ]. Ethanol exposure suppresses mitochondrial dynamics and sensitizes mitochondrial permeability transition pore opening to promote cell death [ 62 ].…”

“…Non-ionic detergents served to permeabilize plasma membrane [ 61 , 62 , 63 ]. The optimization of other commonly used permeabilizing agents included the use of different saponin preparations, digitonin and recombinant lysing solutions such as perfringolysin O [ 64 ].…”

The Genus Cuphea P. Browne as a Source of Biologically Active Phytochemicals for Pharmaceutical Application and Beyond—A Review

“…Antiproliferative and apoptotic activities of methanolic and aqueous extracts of C. aequipetala have been reported for several cancer cell lines: B16F10, HepG2, and MCF-7 [ 128 ]. The methanolic extract induced cell accumulation in G1 phase, DNA fragmentation, and increased caspase-3 activity in B16F10 cells in vitro.…”

Botanical from Piper capense Fruit Can Help to Combat the Melanoma as Demonstrated by In Vitro and In Vivo Studies

“…Rajasekar et al [ 24 ] showed the anticancerous effect of Lithospermum erythrorhizon extract in vitro and in vivo . Uscanga-Palomeque et al [ 25 ] showed the inhibitory effect of Cuphea aequipetala extracts on melanomas in vitro and in vivo . In coherence with these findings, a keen interest in a Cameroonian pharmacopoeia plant called Piper capense from the Piperaceae family was taken into consideration due to its therapeutic virtues, most especially in the treatment of several illnesses like cancer when used in the form of formulation [ 26 , 27 ].…”