The Water Extract of Juniperus communis L. Induces Cell Death and Sensitizes Cancer Cells to Cytostatic Drugs through p53 and PI3K/Akt Pathways

Abstract

Juniper (Juniperus communis L.) is a northern coniferous plant generally used as a spice and for nutritional purposes in foods and drinks. It was previously reported that juniper extract (JE) affects p53 activity, cellular stress, and gene expression induced cell death in human neuroblastoma cells. Therefore, the effects of juniper on p53 and Akt signaling was examined further in A549 lung, 22RV1 and DU145 prostate, and HepG2 liver cancer cells using Western blot, confocal microscopy, and MTT analysis. We found that juniper simultaneously decreased cell viability, activated the p53 pathway, and inactivated the PI3K/Akt pathway. The p53 activation was associated with increased nuclear p53 level. Akt was dephosphorylated, and its inactivation was associated with increased levels of PHLPP1 and PHLPP2 phosphatases. Parallel increases of PARP suggest that JE decreased cell viability by activating cell death. In addition, JE potentiated the effects of gemcitabine and 5-fluorouracil anticancer drugs. Thus, JE can activate cell death in different cancer cell lines through p53 and Akt pathways.

Juniperus communis extract ameliorates lipopolysaccharide‐induced acute kidney injury through the adenosine monophosphate–activated protein kinase pathway

“…NFκB activation induces the expression of cytokines, such as TNF‐α, IL‐1β, and IL‐6, and chemokines, such as CCL2 (Liu et al, 2017). In one study, a water JCo extract inactivated the PI3K–Akt pathway in cancer cells (Raasmaja et al, 2019), and our data revealed that JCo extract suppressed NFκB expression and the downstream expression of chemokines and cytokines such as TNF‐α, IL‐1β, IL‐6, and CCL2 in the rat renal cell line NRK‐52E. In addition to the inflammatory response, LPS induced IL‐1β mRNA expression, controlled by nod‐like receptor protein 3 inflammasome, which is involved in the AMPK–ROS signaling pathway (Wang et al, 2018).…”

Cell cycle arrest and apoptosis induction by Juniperus communis extract in esophageal squamous cell carcinoma through activation of p53‐induced apoptosis pathway

“…Juniperus communis oil contains monoterpene hydrocarbons, such as α‐pinene, myrcene, sabinene, and β‐pinene (Bais et al., 2014; Cabral et al., 2012; Hajdari et al., 2015), most of which are polyphenolic compounds, indicating their anti‐cancer potential. Studies have shown that Juniperus communis L. berry water extracts induces p53‐associated cell apoptosis in human SH‐SY5Y neuroblastoma cells (Lantto et al., 2016), and increases the effect of 5‐FU in non‐small lung cancer A549 cells through regulation of AKT phosphorylation (Raasmaja et al., 2019). In addition, juniper berry oil from Juniperus communis is a chemo‐preventive dietary agent that inhibits cell proliferation and inflammation and induces apoptosis, resulting in suppression of colon tumor formation in azoxymethane‐treated rats (Yaman et al., 2019).…”

Targeting PI3K/Akt signaling in prostate cancer therapy

“…Overall, studies advocate impact of anti‐cancer agents in impairing PI3K/Akt signaling in prostate cancer suppression (Fig. 5) (Abd Wahab et al 2021; Li et al 2018a, b, 2020; Long et al 2021; Zhang et al 2021a, b, c; Chan et al 2017; Raasmaja et al 2019; Sachan et al 2018).…”