Deoxypodophyllotoxin Isolated from Juniperus communis Induces Apoptosis in Breast Cancer Cells

Abstract

The study of anticancer properties from natural products has regained popularity as natural molecules provide a high diversity of chemical structures with specific biological and medicinal activity. Based on a documented library of the most common medicinal plants used by the indigenous people of North America, we screened and isolated compounds with anti-breast cancer properties from Juniperus communis (common Juniper). Using bioassay-guided fractionation of a crude plant extract, we identified the diterpene isocupressic acid and the aryltetralin lignan deoxypodophyllotoxin (DPT) as potent inducers of caspase-dependent programmed cell death (apoptosis) in malignant MB231 breast cancer cells. Further elucidation revealed that DPT, in contrast to isocupressic acid, also concomitantly inhibited cell survival pathways mediated by the MAPK/ERK and NFκB signaling pathways within hours of treatment. Our findings emphasize the potential and importance of natural product screening for new chemical entities with novel anticancer activities. Natural products research complemented with the wealth of information available through the ethnobotanical and ethnopharmacological knowledge of the indigenous peoples of North America can provide new candidate entities with desirable bioactivities to develop new cancer therapies.

Anticancer effect of deoxypodophyllotoxin induces apoptosis of human prostate cancer cells

“…In the present study, DPPT significantly inhibited cell proliferation and cell apoptosis of DU-145 cells in a dose-and time-dependent manner. Several studies indicated that DPPT significantly induced cell apoptosis of HeLa cells (14), breast cancer cells (15) and non-small cell lung cancer cells (16). These results indicated that DPPT may be considered as a drug to target PCa.…”

A Promising Microtubule Inhibitor Deoxypodophyllotoxin Exhibits Better Efficacy to Multidrug-Resistant Breast Cancer than Paclitaxel via Avoiding Efflux Transport

“…Although DPT induced apoptosis of the human BC mDA-MB-231 cell line in vitro (Benzina et al, 2015), little research has been conducted on the efficacy of DPT on the MCF-7 cell line.…”

“…A physiologically based pharmacokinetics model was also established for better efficacy and safety assessment (Chen et al, 2016). Previous studies have demonstrated that DPT exerts an anti-tumor effect on the human BC MDA-MB-231 cell line in vivo and in vitro (Benzina et al, 2015;Khaled et al, 2016). However, the effect of DPT on drug-resistant cancer cells has yet to be investigated.…”

Alternative Treatments for Cancer Prevention and Cure [Part 1]

“…ERK and NFκB signaling pathways within hours of treatment[324]. Antitumor effect of DPT on MDA-MB-231 human breast cancer xenografts in vivo[325] and in vitro[326].…”