Urtica dioica inhibits cell growth and induces apoptosis by targeting Ornithine decarboxylase and Adenosine deaminase as key regulatory enzymes in adenosine and polyamines homeostasis in human breast cancer cell lines

Abstract

Breast cancer is a heterogeneous and multifactorial disease with variable disease progression risk, and treatment response. Urtica dioica is a traditional herb used as an adjuvant therapeutic agent in cancer. In the present study, we have evaluated the effects of the aqueous extract of Urtica dioica on Adenosine deaminase (ADA) and Ornithine decarboxylase (ODC1) gene expression in MCF-7, MDA-MB-231, two breast cancer cell lines being estrogen receptor positive and estrogen receptor negative, respectively. Cell lines were cultured in suitable media. After 24 h, different concentrations of the extract were added and after 72 h, ADA and ODC1 gene expression as well as BCL2 and BAX apoptotic genes were assessed by Taqman real time PCR assay. Cells viability was assessed by MTT assay, and apoptosis was also evaluated at cellular level. The intra and extracellular levels of ODC1 and ADA enzymes were evaluated by ELISA. Results showed differential expression of ADA and ODC1 genes in cancer cell lines. In MCF-7 cell line, the expression level of ADA was upregulated in a dose-dependent manner but its expression did not change in MDA-MB cell line. ODC1 expression was increased in both examined cell lines. Also, increased level of the apoptotic BAX/BCL-2 ratio was detected in MCF-7 cells. These results demonstrated that Urtica dioica induces apoptosis in breast cancer cells by influencing ODC1 and ADA genes expression, and estrogen receptors. The different responses observed with these cell lines could be due to the interaction of Urtica dioica as a phytoestrogen with the estrogen receptor.

Food Bioactives

“…Noteworthy was the increase in the anti-apoptotic Bcl-2 protein; indeed, Bcl-2 can interact with Nur 77/TR3 and convert to Bax-like death effector, subsequently inducing apoptosis [120]. These findings were in agreement with a recent study by Fattahi et al (2018) [121]. In this study, two human breast cancer cell lines, MCF-7 (estrogen and progesterone receptors positive; wild-type P53) and MDA-MB-231 (estrogen and progesterone receptors negative; mutated P53), were treated with U. dioica aqueous extract of leaves.…”

Therapeutic Perspectives of Molecules from Urtica dioica Extracts for Cancer Treatment

“…Noteworthy was the increase in the anti-apoptotic Bcl-2 protein; indeed, Bcl-2 can interact with Nur 77/TR3 and convert to Bax-like death effector, subsequently inducing apoptosis [120]. These findings were in agreement with a recent study by Fattahi et al (2018) [121]. In this study, two human breast cancer cell lines, MCF-7 (estrogen and progesterone receptors positive; wild-type P53) and MDA-MB-231 (estrogen and progesterone receptors negative; mutated P53), were treated with U. dioica aqueous extract of leaves.…”

Nettle Tea Inhibits Growth of Acute Myeloid Leukemia Cells In Vitro by Promoting Apoptosis

“…UD extract enhanced the cytotoxicity of cisplatin in non-small-cell lung cancer H460, H1299, A549, and H322 cell lines through the induction of endoplasmic-reticulum-stress-mediated apoptosis [44]. Furthermore, it activated apoptosis by targeting the ornithine decarboxylase and adenosine deaminase pathway in breast cancer cell lines MCF-7 and MDA-MB-231 [45]. The extract also exerted an apoptotic effect on the AML cell line KG-1 [46].…”