Diosgenin induces cell cycle arrest and apoptosis in HEL cells with increase in intracellular calcium level, activation of cPLA2 and COX-2 overexpression

Abstract

Many natural components of plant extracts are studied for their beneficial effects for health and particularly on carcinogenesis chemoprevention. In the present study, we investigated the effects of diosgenin on erythroleukemia HEL cells. Our results demonstrated that diosgenin induced G2/M arrest of cell cycle progression through p21 up-regulation in a p53-independent pathway and strong induction of apoptosis in HEL cells. Apoptosis induction was accompanied by an increase in Bax/Bcl-2 ratio, PARP cleavage and DNA fragmentation. Moreover, we showed for the first time that diosgenin provoked a collapse of mitochondrial membrane potential with an increase in intracellular calcium levels. It is well known that [Ca2+]i increase is one of the major activators of cytosolic PLA2. In our study, we demonstrated that diosgenin treatment induced cPLA2 activation through translocation to the cellular membrane. Moreover, arachidonic acid metabolism activation led to cyclooxygenase-2 (COX-2) but not lipoxygenase overexpression. Surprisingly, we observed a COX-2 up-regulation associated with apoptosis induction by diosgenin. These findings suggest that diosgenin has a potential chemopreventive effect; future studies should evaluate the mechanism of COX-2 activation during diosgenin-induced apoptosis in cancer cell lines.

MAP kinase subtypes and Akt regulate diosgenin-induced apoptosis of rheumatoid synovial cells in association with COX-2 expression and prostanoid production

“…Particular attention has been given to their potential for cancer chemoprevention, especially as apoptosis inductors (25). Recently, we demonstrated that diosgenin-induced apoptosis in cancer cell lines (26)(27)(28). Furthermore, we described for the first time that diosgenin-induced apoptosis in human RA FLS with COX-2 overexpression (14).…”

Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, IκB kinase activation and NF-κB-regulated gene expression

“…Extracts from these plants have been traditionally used for the treatment of diabetes (Madar et al, 1988;Sharma et al, 1990;Gupta et al, 2001), hypercholestrolemia (Valette et al, 1984;Sauvaire et al, 1991), and gastrointestinal ailments (Pandian et al, 2002;Raju et al, 2004). Research during the last decade has shown that diosgenin suppresses proliferation and induces apoptosis in cells of human colon carcinoma (Raju et al, 2004;Wang et al, 2004), osteosarcoma (Moalic et al, 2001;Corbiere et al, 2003), leukemia (Hibasami et al, 2003;Liu et al, 2005), human erythroleukemia (Leger et al, 2004), and human rheumatoid arthritis . Antiproliferative effects of diosgenin are mediated through cell cycle arrest (Moalic et al, 2001;Liu et al, 2005), disruption of Ca 2 þ homeostasis (Leger et al, 2004;Liu et al, 2005), the activation of p53, release of apoptosis-inducing factor, and modulation of caspase-3 activity .…”

“…Research during the last decade has shown that diosgenin suppresses proliferation and induces apoptosis in cells of human colon carcinoma (Raju et al, 2004;Wang et al, 2004), osteosarcoma (Moalic et al, 2001;Corbiere et al, 2003), leukemia (Hibasami et al, 2003;Liu et al, 2005), human erythroleukemia (Leger et al, 2004), and human rheumatoid arthritis . Antiproliferative effects of diosgenin are mediated through cell cycle arrest (Moalic et al, 2001;Liu et al, 2005), disruption of Ca 2 þ homeostasis (Leger et al, 2004;Liu et al, 2005), the activation of p53, release of apoptosis-inducing factor, and modulation of caspase-3 activity . It also inhibits azoxymethane-induced aberrant colon crypt foci (Raju et al, 2004) and has been shown to inhibit intestinal inflammation (Yamada et al, 1997) and modulate the activity of lipoxygenase (LOX) (Nappez et al, 1995) and cyclooxygenase-2 (COX-2) (Moalic et al, 2001).…”

Diosgenin Inhibits hTERT Gene Expression in the A549 Lung Cancer Cell Line

“…One of the most compounds that founded in fenugreek is Diosgenin with anticancer activity.The study effect of diosgenin on osteosarcoma cells were showed that diosgenin treatment caused an inhibition of 1547 cell growth with a cycle arrest in G1 phase and apoptosis induction and moreover exist a correlation between p53, p21 mRNA expression and nuclear factor-kappaB activation (Moalic et al, 2001). Diosgenin induces cell cycle arrest and apoptosis in HEL cells with increase in intracellular calcium level, activation of cPLA2 and COX-2 overexpression (Leger et al,2004). Another study about diosgenin effect on colon cancer cells showed that diosgenin induces death receptor-5 through activation of p38 pathway and promotes TRAIL-induced apoptosis (Lepage et al, 2011).…”