Pennogenyl Saponins from Paris quadrifolia L. Induce Extrinsic and Intrinsic Pathway of Apoptosis in Human Cervical Cancer HeLa Cells

Abstract

Pennogenyl saponins are the active compounds of large number of plant species and consequently many polyherbal formulations. Hence, great interest has been shown in their characterization and in the investigation of their pharmacological and biological properties, especially anticancer. This present study reports on the evaluation of cytotoxic effects and explanation of the molecular mechanisms of action of the two pennogenyl saponins (PS 1 and PS 2) isolated from Paris quadrifolia L. rhizomes on human cervical adenocarcinoma cell line HeLa. To determine the viability of the cells treated with the compounds we used real-time cell proliferation analysis and found that the pennogenyl saponins PS 1 and PS 2 strongly inhibited the tumor cells growth with IC50 values of 1.11 ± 0.04 μg/ml and 0.87 ± 0.05 μg/ml, respectively. The flow cytometry analysis indicated that the two compounds induced apoptosis in a dose-dependent manner and decreased mitochondrial membrane potential in HeLa cells in the early stage of apoptosis. Quantitative PCR and Western Blot analysis showed that the two saponins significantly increased mRNA expression of FADD and BID as well as induced caspase-8 via increased of procaspase-8 processing in the treated cells. The results of this study suggest that both the extrinsic death receptor and intrinsic mitochondrial pathways are involved in the programmed cell death.

Curcumin enhances the anti‐cancer effects of Paris Saponin II in lung cancer cells

“…For they were more sensitive in SCLC (NCI‐H446) than that in other cells based on several assays, cell cycle assay and cytokine antibody microarray analyses in NCI‐H446 cancer cells were carried out. The main pathways involved in the cell apoptosis were the extrinsic death receptor pathway and intrinsic mitochondria pathway . According to the cytokine antibody microarray analyses in NCI‐H446 cancer cells, the combination of PSII and CUR mainly induced extrinsic death receptor pathway involved in the programmed cell death (Table ).…”

“…The main pathways involved in the cell apoptosis were the extrinsic death receptor pathway and intrinsic mitochondria pathway. 21 According to the cytokine antibody microarray analyses in NCI-H446 cancer cells, the combination of PSII and CUR mainly induced extrinsic death receptor pathway involved in the programmed cell death (Table 3). Combination treatment activated the death receptors such as TNFα, FasL, DR6 and CD40/CD40L to increase the protein expression of caspase 3 and then induced apoptosis ( Figure 8).…”

Combining doxorubicin with a phenolic extract from flaxseed oil: Evaluation of the effect on two breast cancer cell lines

“…Loss of the mitochondrial inner transmembrane potential is a reliable indicator of mitochondrial dysfunction and cellular health. This effect is often observed to be associated with the early stages of apoptosis (18). We observed in MCF-7 cell line an increase of the mean percentage of cellular depolarization in presence of IC 50 concentrations for PEFSO and Dox, respectively, when compared to untreated.…”

Securinine from Phyllanthus glaucus Induces Cell Cycle Arrest and Apoptosis in Human Cervical Cancer HeLa Cells

“…The maximal concentrations of the solvents used in all the MTT experiments were 5.0% (v/v) and 1.0% (v/v) for methanol and DMSO, respectively. Following treatment, the cells were prepared as described previously [16]. The absorption of the obtained formazan solution was measured with a plate reader (Epoch, BioTek Instruments, USA).…”

“…The cells were treated with securinine in the final concentration range of 1.0–50.0 μg/ml for 24 h. The concentration of securinine solvent (DMSO) did not exceed 0.5% (v/v). After 24 h, the cells were stained according to previously described protocol [16] and observed under a fluorescent microscope (Leica, Switzerland).…”