Silver nanoparticles enhance the apoptotic potential of gemcitabine in human ovarian cancer cells: combination therapy for effective cancer treatment

Abstract

Background Gemcitabine (GEM) is widely used as an anticancer agent in several types of solid tumors. Silver nanoparticles (AgNPs) possess unique cytotoxic features and can induce apoptosis in a variety of cancer cells. In this study, we investigated whether the combination of GEM and AgNPs can exert synergistic cytotoxic effects in the human ovarian cancer cell line A2780. Methods We synthesized AgNPs using resveratrol as a reducing and stabilizing agent. The synthesized nanomaterials were characterized using various analytical techniques. The anticancer effects of a combined treatment with GEM and AgNPs were evaluated using a series of cellular assays. The expression of pro- and antiapoptotic genes was measured using real-time reverse transcription polymerase chain reaction. Apoptosis was confirmed by TUNEL assay. Results In this study, combined treatment with GEM and AgNPs significantly inhibited viability and proliferation in A2780 cells. Moreover, the levels of apoptosis in cells treated with a combination of GEM and AgNPs were significantly higher compared with those in cells treated with GEM or AgNPs alone. Our data suggest that GEM and AgNPs exhibit potent apoptotic activity in human ovarian cancer cells. Combined treatment with GEM and AgNPs showed a significantly higher cytotoxic effect in ovarian cancer cells compared with that induced by either of these agents alone. Conclusion Our study demonstrated that the interaction between GEM and AgNPs was cytotoxic in ovarian cancer cells. Combined treatment with GEM and AgNPs caused increased cytotoxicity and apoptosis in A2780 cells. This treatment may have therapeutic potential as targeted therapy for the treatment of ovarian cancer. To our knowledge, this study could provide evidence that AgNPs can enhance responsiveness to GEM in ovarian cancer cells and that AgNPs can potentially be used as chemosensitizing agents in ovarian cancer therapy.

Cytotoxic Potential and Molecular Pathway Analysis of Silver Nanoparticles in Human Colon Cancer Cells HCT116

“…Therefore, we measured the impact of AgNPs on dead-cell protease activity in HCT116 cells exposed to various concentrations of AgNPs; the cell viability was calculated according to the manufacturer’s instructions (Promega Corp., G9292, WI, USA) and a previously reported method [44]. HCT116 cells treated with AgNPs showed reduced viability with increasing concentrations of AgNPs (Figure 3B).…”

Delivery of a TNF‐α–derived peptide by nanoparticles enhances its antitumor activity by inducing cell‐cycle arrest and caspase‐dependent apoptosis

“…Nanomaterials are currently used extensively as drug carriers for cancer treatment (17,18). Thus far, a variety of nanomaterials with different functions, such as polymers, mesoporous silica, and carbon nanotubes, have been developed for cancer treatment (19)(20)(21). Among these nanomaterials, selenium nanoparticles (SeNPs) are attracting increasing attention as potential drug nanocarriers because of their lower toxicity, more robust biologic activities, and higher bioavailability than organic or inorganic selenocompounds (22,23).…”

Graphene oxide-silver nanocomposites induce oxidative stress and apoptosis in caprine fetal fibroblast cells

“…One of the main mechanisms of toxicity induced by nanomaterial is that it causes oxidative stress through the generation of ROS and causes damage to cellular components including DNA damage, abnormal activation of transcription factors, depletion of antioxidant molecules, binding and disabling of proteins, and damage to the cell membrane [26]. Oxidative stress inducing ROS is one of the proposed toxicological mechanisms of various nanomaterials such as Ag or Ag-graphene nanocomposites, can cause mitochondrial damage, and initiation of lipid peroxidation [42,45,46]. Cytotoxicity of AgNPs is associated with increased production of ROS, which play an important role in apoptosis induced by AgNPs [47].…”

“…Many type of cells treated with AgNPs and GO showed signi cantly increased levels of MDA, which is one of the nal products of polyunsaturated fatty acids peroxidation in the cells [17,30,[49][50][51]. Assessing the release of intracellular LDH in cell, which resulted from the breakdown and alteration in the permeability of the plasma membrane, is one of marker for estimating cytotoxicity [30,46]. rGO-Ag increases LDH leakage in human cancer cells, thus resulting in cell death [30,42,52].…”