Ferruginol induced apoptosis on SK-Mel-28 human malignant melanoma cells mediated through P-p38 and NF-κB

Abstract

<jats:p> In the present investigation, the antitumor effect of ferruginol (FGL) in SK-Mel-28 human malignant melanoma cells was studied. To investigate the cytotoxic property of FGL, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used. Results revealed that prolonged treatment duration decreases the IC<jats:sub>25</jats:sub>, IC<jats:sub>50</jats:sub>, and IC<jats:sub>75</jats:sub> concentrations of FGL. The cytotoxicity was further confirmed by lactate dehydrogenase assay. As evident from comet assay, FGL induces DNA damage in a dose-dependent manner. Annexin V and 7-ADD assays showed that FGL-induced DNA damage triggers apoptosis-mediated cell death as confirmed by caspase-3 activity assay. As seen through Western blotting, FGL increases phosphorylation of p38 and nuclear translocation of NF-κB. Further, it was observed that p38 phosphorylation is responsible for NF-κB translocation to the nucleus. Further, inhibition of p38 phosphorylation and translocation of NF-κB decrease caspase-3 activity. The above finding confirms that caspase-3 activation is mediated through P-p38 and nuclear translocation of NF-κB. The present findings indicate that FGL significantly suppresses the proliferation of SK-Mel-28 cells in a dose- and time-dependent manner through induction of apoptosis. Furthermore, FGL executes apoptosis through phosphorylation of key protein such as p38 and translocation of NF-κB into the nucleus. </jats:p>

Ferruginol Diterpenoid Selectively Inhibits Human Thyroid Cancer Growth by Inducing Mitochondrial Dependent Apoptosis, Endogenous Reactive Oxygen Species (ROS) Production, Mitochondrial Membrane Potential Loss and Suppression of Mitogen-Activated Protein Kinase (MAPK) and PI3K/AKT Signaling Pathways

“…cells. These results agreed with investigations that reported that ferruginol inhibited the growth of ovarian carcinoma cells and melanoma cells [16,17]. Compounds of plant origin have been shown to halt the growth of cancer cells through multiple mechanisms such as apoptosis, cell cycle arrest, and autophagy [18].…”

Biological Profiling of Semisynthetic C19-Functionalized Ferruginol and Sugiol Analogues

“…To sum up, we have carried out the first chemical synthesis of the abietane (+)-4-epi-liquiditerpenoic acid A (8a). It was prepared in a short synthetic sequence of five steps in 10% overall yield from methyl callitrisate (7). Two parallel routes led to several oxidized analogs, such as naturally occurring lambertic acid (13) or 19-hydroxyferruginol (14).…”

“…The tested compounds 8a and 9-16 were obtained from (+)-methyl callitrisate (7), which was obtained from callitrisic acid (6) extracted from Sandarac resin [18], as shown in Scheme 1. Compounds 8a, 15 and 16 are novel derivatives.…”

“…Intraperitoneal administration of ferruginol considerably inhibited the growth of subcutaneous cancer xenograft models [5]. Ferruginol (1) also displays antiproliferative properties in human ovarian cancer and malignant melanoma cells by inhibiting cancer cell migration and inducing apoptosis [6,7], as well as in human thyroid cancer cells [8]. The corresponding C7-oxidized sugiol (2) has shown in vitro cytotoxic activity against human pancreatic and melanoma tumor cell models [9], antitumor activity against EBV-EA activation [10], and in vivo antitumor properties in a prostate DU145 xenograft murine model [11].…”

The Search for Putative Hits in Combating Leishmaniasis: The Contributions of Natural Products Over the Last Decade

“…Elucidation of the exact mechanism of action of four triterpenes from the roots of Salvia deserta showed that despite the strong antioxidant capacity of 93, it also kill parasites by inhibiting isopentenyl diphosphate condensation with the major target being farnesyl diphosphate synthase [110]. Studies to also understand the molecular basics of 94 shows a similar action like 80, but fragmentation of DNA strands has been described for diterpene 95 and 96 [111,112]. Inhibition of oxidative pathways particularly IFN-γ-related signaling by similar diterpenoid quinones isolated from the roots of Salvia officinalis has also been shown to prevent disease proliferation and further protecting the host specie [113].…”