Curcuma wenyujin Extract Induces Apoptosis and Inhibits Proliferation of Human Cervical Cancer Cells In Vitro and In Vivo

Abstract

An essential oil extract, derived from the rhizome of Curcuma wenyujin (CWE), possesses antioxidative, antimicrobial, and anti-inflammatory properties. However, it remains unknown how exactly CWE inhibits tumor growth. In this study, using human cervical cancer HeLa cells, the authors postulated that CWE has the ability to inhibit tumor growth. The study shows that CWE dose-dependently suppressed colony formation and inhibited the proliferation of HeLa cells through blockade of cell cycle progression at G1 phase and apoptosis. CWE-induced G1 arrest was associated with retinoblastoma protein dephosphorylation and reduced amounts of cyclins D1 and D3, and cyclin-dependent kinase 4 and 6 proteins. CWE treatment resulted in apoptosis in HeLa cells as evidenced by morphological changes, caspase activation and PARP cleavage, which can be reversed by a pan-caspase inhibitor. It was observed that CWE treatment activated the mitochondrial apoptotic pathway indicated by a decrease in Mcl-1 and Bcl-xL levels, resulting in mitochondrial membrane potential loss and caspases 9 activation. CWE-treated cells displayed reduced PTEN, AKT, and STAT3 phosphorylation and downregulation of NFkB signaling, providing a mechanism for the G1 arrest and apoptosis observed. Furthermore, CWE inhibited tumor growth of HeLa in a xenograft mouse tumor model, suggesting that CWE inhibited tumorigenesis by inhibiting cell proliferation and inducing apoptosis. These findings are the first to reveal the molecular basis for the anticervical cancer action of CWE. The results suggest that CWE could be developed as a drug for the management of cervical cancer.

Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA

“…Thus, signaling pathways involved in enhancing apoptosis are potential targets for identifying innovative drug candidates. There are a number of previous reports demonstrating that the oily extracts of C. wenyujin induce cellular apoptosis and inhibit proliferation in certain cancer cell lines (10,(28)(29)(30). The present study focused on curcumol, one of the active compounds isolated from the curcuma oil (12).…”

Turmeric enhancing anti-tumor effect of Rhizoma paridis saponins by influencing their metabolic profiling in tumors of H22 hepatocarcinoma mice

“…Turmeric as a common food belonging to Curcuma longa showed anti-inflammatory, antitumor and antioxidative properties [8]. Curcuminoids, as its main active compounds, increased the accumulation of drug through the interactions at the substrate-binding sites [1].…”

Conservation and population genetic diversity of Curcuma wenyujin (Zingiberaceae), a multifunctional medicinal herb

“…C. wenyujin rhizome extract contains a variety of bioactive ingredients, such as curdione (Xia et al, 2012), aurantiamide (Ma et al, 2009;Xia et al, 2012), and sesquiterpene (Sun et al, 2009;Dong et al, 2013;Zhu et al, 2013a). These substances can not only induce apoptosis (Xiao et al, 2008;Lim et al, 2010), inhibit platelet aggregation (Xia et al, 2012), and tumor growth (Sun et al, 2009;Lim et al, 2010), but also serve as clinical agents of anti-oxidation, anti-microbial action (Dong et al, 2013;Zhu et al, 2013b), and anti-inflammation (Tohda et al, 2006).…”

“…Mohanty et al (2011) assessed the genetic stability of micropropagated Zingiber rubens by using RAPD and ISSR markers, and found that the duration of the culture period (more than two years) did not affect the plants' genetic integrity; Das et al (2011) determined the genetic diversity and molecular classification of nine Curcuma species from northeast India using DNA fingerprinting (ISSR, RAPD, and amplified fragment length polymorphism). However, in the case of C. wenyujin, previous studies have mainly focused on the isolation and characterization of the plant's bioactive ingredients (Xia et al, 2012;Zhu et al, 2013a), as well as their functions (Sun et al, 2009;Lim et al, 2010;Zhu et al, 2013b). Only three studies have been conducted on the genetic diversity (or variation) of C. wenyujin using single DNA markers (RAPD or ISSR) (Tao et al, 2007(Tao et al, , 2009Wang et al, 2008).…”