Selaginella tamariscina Induces Apoptosis via a Caspase-3-Mediated Mechanism in Human Promyelocytic Leukemia Cells

Abstract

Cell apoptosis is now known to play an important role in the maintenance of cellular homeostasis and anticarcinogenesis. Selaginella tamariscina (ST) is a traditional medicinal plant for treatment of advanced cancer in the Orient. In the present study, the anticancer effect of ST was investigated by analyzing its potential to induce apoptosis in human leukemia HL-60 cells. ST-induced cytotoxicity of HL-60 cells was monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The apoptosis was determined by microscopic examination of apoptotic morphology, determination of DNA fragmentation by electrophoresis, activation of caspase-3, and protein expression of procaspase-3, poly(ADP-ribose) polymerase (PARP) cleavage, Bcl-2, and Bax. ST was cytotoxic to HL-60 cells in a dose-dependent manner. However, ST-induced cytotoxicity was suppressed by reactive oxygen species scavengers, including superoxide dismutase (SOD) and catalase. ST caused DNA fragmentation and nuclear condensation, all characteristics of apoptosis. ST-induced apoptosis is accompanied by the activation of caspase-3 and the specific proteolytic cleavage of PARP. Concomitantly, ST treatments led to an increase in the proapoptotic Bax levels, while Bcl-2 expression was decreased. Moreover, this effect was attenuated by SOD and catalase. These results suggest that oxidative stress may be involved in the cytotoxicity of ST, and that ST-induced apoptosis of HL-60 cells is primarily mediated by the caspase activation pathway.

Phytochemicals from fern species: potential for medicine applications

“…Spring was shown to exhibit anti-metastatic properties that resulted from the down-regulation of metalloproteinases and reduced activation of an Akt kinase . In this context, it is interesting that an earlier report had suggested that caspase-3 plays a functional role in S. tamariscina-induced apoptosis in leukemia cells (Ahn et al 2006). Phytochem Rev (2017 Antidiabetic activity S. tamariscina extracts have also been shown to exert anti-hyperglycemic effects in diabetic rats and HepG2 cells (Zheng et al 2011a).…”

Ferns and Lycopods—A Potential Treasury of Anticancer Agents but Also a Carcinogenic Hazard

“…Moreover, the water fraction of the extract increased p53 gene expression in U937 cells and induced G 1 cell cycle arrest in A2780 cells (ovarian) with a wild type p53 gene, but not in HT‐29 cells (colon), where p53 is mutant (Lee et al ., ). Interestingly, the cytotoxic and pro‐apoptotic effects of S. tamariscina on HL‐60 cells were attenuated by superoxide dismutase and catalase, enzymes which scavenge reactive oxygen species (ROS) (Ahn et al ., ). On the other hand, extracts from S .…”

Comparison of cytotoxic activities of extracts from Selaginella species

“…have been reported to show antitumor and antioxidant properties. The antitumor mechanisms are related to induction of apoptosis through deoxyribonucleic acid (DNA) fragmentation and nucleus clotting[ 10 ] or through blockade of fatty acid synthesis,[ 8 ] inducing expression of p53 and G1 arrest,[ 11 ] inhibiting transactivation of iNOS and COX-2 through inactivate NF-kB and prevent translocation of p65. [ 12 ]…”