Abstract
BackgroundThevetia peruviana (Pers.) K. Schum or Cascabela peruviana (L.) Lippold (commonly known as ayoyote, codo de fraile, lucky nut, or yellow oleander), native to Mexico and Central America, is a medicinal plant used traditionally to cure diseases like ulcers, scabies, hemorrhoids and dissolve tumors. The purpose of this study was to evaluate the cytotoxic, antiproliferative and apoptotic activity of methanolic extract of T. peruviana fruits on human cancer cell lines.MethodsThe cytotoxic activity of T. peruviana methanolic extract was carried out on human breast, colorectal, prostate and lung cancer cell lines and non-tumorigenic control cells (fibroblast and Vero), using the MTT assay. For proliferation and motility, clonogenic and wound-healing assays were performed. Morphological alterations were monitored by trypan blue exclusion, as well as DNA fragmentation and AO/EB double staining was performed to evaluate apoptosis. The extract was separated using flash chromatography, and the resulting fractions were evaluated on colorectal cancer cells for their cytotoxic activity. The active fractions were further analyzed through mass spectrometry.ResultsThe T. peruviana methanolic extract exhibited cytotoxic activity on four human cancer cell lines: prostate, breast, colorectal and lung, with values of IC50 1.91 ± 0.76, 5.78 ± 2.12, 6.30 ± 4.45 and 12.04 ± 3.43 μg/mL, respectively. The extract caused a significant reduction of cell motility and colony formation on all evaluated cancer cell lines. In addition, morphological examination displayed cell size reduction, membrane blebbing and detachment of cells, compared to non-treated cancer cell lines. The T. peruviana extract induced apoptotic cell death, which was confirmed by DNA fragmentation and AO/EB double staining. Fractions 4 and 5 showed the most effective cytotoxic activity and their MS analysis revealed the presence of the secondary metabolites: thevetiaflavone and cardiac glycosides.ConclusionT. peruviana extract has potential as natural anti-cancer product with critical effects in the proliferation, motility, and adhesion of human breast and colorectal cancer cells, and apoptosis induction in human prostate and lung cancer cell lines, with minimal effects on non-tumorigenic cell lines.
Highlights
IntroductionSchum or Cascabela peruviana (L.) Lippold (commonly known as ayoyote, codo de fraile, lucky nut, or yellow oleander), native to Mexico and Central America, is a medicinal plant used traditionally to cure diseases like ulcers, scabies, hemorrhoids and dissolve tumors
Cytotoxic activity of T. peruviana fruit methanol extract on human prostate, breast, colorectal, and lung cancer cell lines In order to assess the cytotoxic effect of the T. peruviana methanol extract on breast (HTB-22), colorectal (HTB-38), prostate (HTB-81), and lung (HTB-177) cancer cell lines, a MTT assay was performed
The criteria of cytotoxicity established by the U.S National Cancer Institute (NCI) considers a crude extract as active, moderately active, or inactive, when the Half maximal inhibitory concentration (IC50) values are lower than 20 μg/mL, from 20 to 100 μg/mL, or higher than 100 μg/mL, respectively [23]
Summary
Schum or Cascabela peruviana (L.) Lippold (commonly known as ayoyote, codo de fraile, lucky nut, or yellow oleander), native to Mexico and Central America, is a medicinal plant used traditionally to cure diseases like ulcers, scabies, hemorrhoids and dissolve tumors. The purpose of this study was to evaluate the cytotoxic, antiproliferative and apoptotic activity of methanolic extract of T. peruviana fruits on human cancer cell lines. The anticancer potential of parts of T. peruviana plant, such as leaves, bark and seeds has been evaluated against human gastric and pancreatic cancer cell lines [11], the anticancer potential of T. peruviana fruit is still unknown because only a few cardiac glycosides have been identified and examined as cytotoxic agents. The T. peruviana fruit extract has been investigated in this study to explore its anticancer potential against the most common cancer types (lung, breast, prostate and colorectal), in terms of morphological analysis, motility and cell adhesive properties, DNA damage and induction of apoptosis in human cancer cell lines
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