Dr. Weeks’ Comment; Ambrosia arborescens is a weed – the bane of many peoples’ existence because of the allergic watery eyes and runny noses it creates – it is, in common name, the RAGWEED. Like the other horrible weed which infiltrates into many a garden and overcomes other usefuil plant, the morning glory (bindweed) it contains powerful anti-cancer agents: sesquiterpene lactones in the case of ragweed and Ipomoeassin compounds in the case of the morning glory. Here below we see that the ragweed also has the all important anticancer STEM cellproperties as well. Of course, these anti- cancer STEM cell properties are driven by anti-inflammatory forces such as “ inhibited tumour necrosis factor-α-induced translocation of NF-κB from the cytoplasm to the nucleus. Damsin and ambrosin treatment increased the number of micronuclei; moreover, another sign of DNA damage was the increased level of p53.”.
Otherwise stated: “…the chemical and biological properties of SLs that lead to enhanced anticancer and anti-inflammatory effects…”
Anti-cancer stem cell activity of a sesquiterpene lactone isolated from Ambrosia arborescens and of a synthetic derivative
Wendy Soria Sotillo, et al PLOS Sept 1 2017
SOURCE https://doi.org/10.1371/journal.pone.0184304
Abstract
New regimens are constantly being pursued in cancer treatment, especially in the context of treatment-resistant cancer stem cells (CSCs) that are assumed to be involved in cancer recurrence.
Here, we investigated the anti-cancer activity of sesquiterpene lactones (SLs) isolated from Ambrosia arborescens and of synthetic derivatives in breast cancer cell lines, with a specific focus on activity against CSCs. The breast cancer cell lines MCF-7, JIMT-1, and HCC1937 and the normal-like breast epithelial cell line MCF-10A were treated with the SLs damsin and coronopilin, isolated from A. arborescens, and with ambrosin and dindol-01, synthesized using damsin. Inhibitory concentration 50 (IC50) values were obtained from dose-response curves. Based on IC50 values, doses in the μM range were used for investigating effects on cell proliferation, cell cycle phase distribution, cell death, micronuclei formation, and cell migration. Western blot analysis was used to investigate proteins involved in cell cycle regulation as well as in the NF-κB pathway since SLs have been shown to inhibit this transcription factor. Specific CSC effects were investigated using three CSC assays. All compounds inhibited cell proliferation; however, damsin and ambrosin were toxic at single-digit micromolar ranges, while higher concentrations were required for coronopilin and dindol-01. Of the four cell lines, the compounds had the least effect on the normal-like MCF-10A cells. The inhibition of cell proliferation can partly be explained by downregulation of cyclin-dependent kinase 2. All compounds inhibited tumour necrosis factor-α-induced translocation of NF-κB from the cytoplasm to the nucleus. Damsin and ambrosin treatment increased the number of micronuclei; moreover, another sign of DNA damage was the increased level of p53. Treatment with damsin and ambrosin decreased the CSC subpopulation and inhibited cell migration. Our results suggest that these compounds should be further investigated to find efficient CSC-inhibiting compounds.
AND
Anticancer Res. 2013 Sep;33(9):3799-805.
Multiple anticancer effects of damsin and coronopilin isolated from Ambrosia arborescens on cell cultures.
Villagomez R1, et al
Abstract
Terpenoids in plants are important sources for drug discovery. In this study, we extracted damsin and coronopilin, two sesquiterpene lactones, from Ambrosia arborescens and examined their anticancer effects on cell cultures. Damsin and coronopilin inhibited cell proliferation, DNA biosynthesis and formation of cytoplasmic DNA histone complexes in Caco-2 cells, with damsin being more potent than coronopilin. Further studies using the luciferase reporter system showed that damsin and coronopilin also inhibited expressions of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT3), indicating that these sesquiterpenes can interfere with NF-κB and STAT3 pathways. Finally, we examined the effects of two synthetic dibrominated derivatives of damsin, 11α,13-dibromodamsin and 11β,13-dibromodamsin. While bromination appeared to weaken the antiproliferative effects of damsin, the β epimer had strong inhibitory effects on STAT3 activation. In conclusion, the sesquiterpene lactones damsin and coronopilin have inhibitory effects on cell proliferation, DNA biosynthesis and NF-κB and STAT3 pathways, thus being potentially important for discovery of drugs against cancer.
What made sesquiterpene lactones reach cancer clinical trials?
Abstract
Sesquiterpene lactones (SLs) are plant-derived compounds often used in traditional medicine against inflammation and cancer. This review focuses on the chemical and biological properties of SLs that lead to enhanced anticancer and anti-inflammatory effects. The chemical properties comprise alkylating center reactivity, lipophilicity, and molecular geometry and electronic features. SLs in clinical trials are artemisinin, thapsigargin and parthenolide and many of their synthetic derivatives. These drugs are selective toward tumor and cancer stem cells by targeting specific signaling pathways, which make them lead compounds in cancer clinical trials.