Ethanolic Extract of Senna velutina Roots: Chemical Composition, In Vitro and In Vivo Antitumor Effects, and B16F10-Nex2 Melanoma Cell Death Mechanisms

Abstract

Cutaneous melanoma is among the most aggressive types of cancer, and its rate of occurrence increases every year. Current pharmacological treatments for melanoma are not completely effective, requiring the identification of new drugs. As an alternative, plant-derived natural compounds are described as promising sources of new anticancer drugs. In this context, the objectives of this study were to identify the chemical composition of the ethanolic extract of Senna velutina roots (ESVR), to assess its in vitro and in vivo antitumor effects on melanoma cells, and to characterize its mechanisms of action. For these purposes, the chemical constituents were identified by liquid chromatography coupled to high-resolution mass spectrometry. The in vitro activity of the extract was assessed in the B16F10-Nex2 melanoma cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and based on the apoptotic cell count; DNA fragmentation; necrostatin-1 inhibition; intracellular calcium, pan-caspase, and caspase-3 activation; reactive oxygen species (ROS) levels; and cell cycle arrest. The in vivo activity of the extract was assessed in models of tumor volume progression and pulmonary nodule formation in C57Bl/6 mice. The chemical composition results showed that ESVR contains flavonoid derivatives of the catechin, anthraquinone, and piceatannol groups. The extract reduced B16F10-Nex2 cell viability and promoted apoptotic cell death as well as caspase-3 activation, with increased intracellular calcium and ROS levels as well as cell cycle arrest at the sub-G0/G1 phase. In vivo, the tumor volume progression and pulmonary metastasis of ESVR-treated mice decreased over 50%. Combined, these results show that ESVR had in vitro and in vivo antitumor effects, predominantly by apoptosis, thus demonstrating its potential as a therapeutic agent in the treatment of melanoma and other types of cancer.

An Insight into Anticancer Effect of Propolis and Its Constituents: A Review of Molecular Mechanisms

“…Furthermore, propolis modulates the inflammatory microenvironment and induces apoptosis by inhibiting TLR4 singling [93]. In another study, Turkish ethanolic propolis extract induces apoptosis by upregulating proapoptotic protein levels and alters the oncogenic and tumor suppressor gene expression in breast cancer cell lines [94]. A recent report suggested that red propolis along with L-lysine reduces tumor angiogenesis and tumor growth in hamster cheek pouch walker 256 cancer cell-inoculated cancer model [95].…”

Medicinal Plants from Brazilian Cerrado: Antioxidant and Anticancer Potential and Protection against Chemotherapy Toxicity

“…Furthermore, these features were reversed by chelation of calcium, demonstrating the involvement of calcium as the main regulator of cell death mediated by S. velutina . Castro et al [142] evaluated the effect of an extract from the roots of S. velutina on a melanoma cell line B16F10-Nex2 and also evaluated the antimetastatic effect of this extract using models of tumour volume progression and pulmonary nodule formation in C57Bl/6 mice. The extract reduced cell viability and promoted apoptotic cell death, caspase-3 activation, with increased intracellular calcium and ROS levels, and cell cycle arrest at the sub-G0/G1 phase.…”

“…Gallic acid induces death in various cell lines via the intrinsic apoptotic pathway [79–81]. S. velutina also has a large number of phenolic compounds; specifically, the phytochemical analysis of roots identified flavonoid-like molecules, such as epigallocatechin, epicatechin, rutin, kaempferol glycosides, and dimeric and trimeric proanthocyanidins [18], and identified the main compounds to be the flavonoid derivatives of catechin and piceatannol (active metabolite of resveratrol) groups and dimeric tetrahydroanthracene derivatives [142].…”

SEC23A Inhibit Melanoma Metastatic through Secretory PF4 Cooperation with SPARC to Inhibit MAPK Signaling Pathway

“…Cutaneous melanoma (CM) is a key form of malignancy of the skin 1 . According to the World Health Organization, approximately 132,000 cases of melanoma are diagnosed every year worldwide 2 . It is largely responsible for the skin cancer related death 1 , 3 .…”