Combination of salinomycin and silver nanoparticles enhances apoptosis and autophagy in human ovarian cancer cells: an effective anticancer therapy

Abstract

Ovarian cancer is one of the most important malignancies, and the origin, detection, and pathogenesis of epithelial ovarian cancer remain elusive. Although many cancer drugs have been developed to dramatically reduce the size of tumors, most cancers eventually relapse, posing a critical problem to overcome. Hence, it is necessary to identify possible alternative therapeutic approaches to reduce the mortality rate of this devastating disease. To identify alternative approaches, we first synthesized silver nanoparticles (AgNPs) using a novel bacterium called Bacillus clausii . The synthesized AgNPs were homogenous and spherical in shape, with an average size of 16–20 nm, which are known to cause cytotoxicity in various types of human cancer cells, whereas salinomycin (Sal) is able to kill cancer stem cells. Therefore, we selected both Sal and AgNPs to study their combined effect on apoptosis and autophagy in ovarian cancer cells. The cells treated with either Sal or AgNPs showed a dose-dependent effect with inhibitory concentration (IC)-50 values of 6.0 µM and 8 µg/mL for Sal and AgNPs, respectively. To determine the combination effect, we measured the IC 25 values of both Sal and AgNPs (3.0 µM and 4 µg/mL), which showed a more dramatic inhibitory effect on cell viability and cell morphology than either Sal or AgNPs alone. The combination of Sal and AgNPs had more pronounced effect on cytotoxicity and expression of apoptotic genes and also significantly induced the accumulation of autophagolysosomes, which was associated with mitochondrial dysfunction and loss of cell viability. Our data show a strong synergistic interaction between Sal and AgNPs in tested cancer cells. The combination treatment increased the therapeutic potential and demonstrated the relevant targeted therapy for the treatment of ovarian cancer. Furthermore, we provide, for the first time, a mode of action for Sal and AgNPs in ovarian cancer cells: enhanced apoptosis and autophagy.

Silver nanoparticles of different sizes induce a mixed type of programmed cell death in human pancreatic ductal adenocarcinoma

“…However, it has to be noticed that synergism between nanoparticles and autophagy may improve existing cancer therapies [ 84 ]. Several studies indicated that elevated autophagy after nanoparticles treatment leads to increased tumor cell death [ 85 ]. Li et al [ 12 ], concluded that activation of both autophagy and apoptosis by nanoparticles suggests that nanoparticle-induced autophagy causes irreversible cellular damage.…”

Role of Oxidative and Nitro‐Oxidative Damage in Silver Nanoparticles Cytotoxic Effect against Human Pancreatic Ductal Adenocarcinoma Cells

“…In recent years, numerous studies have claimed that AgNPs, due to their unique cytotoxic features, size- and shape-depending, antiproliferative, and apoptosis-inducing activity, can be successfully used as antitumor agents [ 3 – 5 ]. Indeed, AgNP-induced cancer cell death by apoptosis, necroptosis, autophagy, and necrosis have been observed [ 6 , 7 ]. However, the molecular mechanism involved in the cytotoxicity of AgNPs against cancer cells is still underway to clarify [ 8 ].…”

Nrf2 promotes progression of non-small cell lung cancer through activating autophagy

“…Recent studies strongly support the relevance of the interplay between autophagy and apoptosis. [22][23][24] Our result discovered that inhibition of autophagy via 3-MA increased the proportion of apoptotic 95D-Nrf2 cells, meaning that autophagy may potentially involve in Nrf2-associated activities in NSCLC. Then we detected changes of autophagy biomarkers in Nrf2 upregulated or downregulated cell lines, and these autophagy biomarkers dramatically changes in Nrf2 upregulated or downregulated cell lines.…”