Novel biomolecule lycopene-reduced graphene oxide-silver nanoparticle enhances apoptotic potential of trichostatin A in human ovarian cancer cells (SKOV3)

Abstract

Background Recently, there has been much interest in the field of nanomedicine to improve prevention, diagnosis, and treatment. Combination therapy seems to be most effective when two different molecules that work by different mechanisms are combined at low dose, thereby decreasing the possibility of drug resistance and occurrence of unbearable side effects. Based on this consideration, the study was designed to investigate the combination effect of reduced graphene oxide-silver nanoparticles (rGO-AgNPs) and trichostatin A (TSA) in human ovarian cancer cells (SKOV3). Methods The rGO-AgNPs were synthesized using a biomolecule called lycopene, and the resultant product was characterized by various analytical techniques. The combination effect of rGO-Ag and TSA was investigated in SKOV3 cells using various cellular assays such as cell viability, cytotoxicity, and immunofluorescence analysis. Results AgNPs were uniformly distributed on the surface of graphene sheet with an average size between 10 and 50 nm. rGO-Ag and TSA were found to inhibit cell viability in a dose-dependent manner. The combination of rGO-Ag and TSA at low concentration showed a significant effect on cell viability, and increased cytotoxicity by increasing the level of malondialdehyde and decreasing the level of glutathione, and also causing mitochondrial dysfunction. Furthermore, the combination of rGO-Ag and TSA had a more pronounced effect on DNA fragmentation and double-strand breaks, and eventually induced apoptosis. Conclusion This study is the first to report that the combination of rGO-Ag and TSA can cause potential cytotoxicity and also induce significantly greater cell death compared to either rGO-Ag alone or TSA alone in SKOV3 cells by various mechanisms including reactive oxygen species generation, mitochondrial dysfunction, and DNA damage. Therefore, this combination chemotherapy could be possibly used in advanced cancers that are not suitable for radiation therapy or surgical treatment and facilitate overcoming tumor resistance and disease progression.

Cytotoxicity and Transcriptomic Analysis of Silver Nanoparticles in Mouse Embryonic Fibroblast Cells

“…These elevations might contribute to AgNPs-mediated oxidative stress, which is the major cause of DNA damage. Previous studies demonstrated that oxidative stress can induce DNA fragmentation, single-strand breaks in human breast cancer cells, and double-strand breaks in ovarian cancer cells [ 9 , 71 ]. Another study reported that HT22 hippocampal neuronal cells exposed to AgNPs for 24 h displayed effects on various cellular processes by alteration of p53, p21, and lamin B1, as well as methylation changes [ 18 ].…”

Anticancer Properties of Platinum Nanoparticles and Retinoic Acid: Combination Therapy for the Treatment of Human Neuroblastoma Cancer

“…Similarly, the combination of silver nanoparticles and HDAC inhibitor increased the leakage of protease in human alveolar basal epithelial cells [63]. In addition, the combination of graphene oxide-silver nanoparticles and trichostatin A enhanced the leakage of intracellular protease in human ovarian cancer cells [65], and RA increased the leakage of LDH in F9 teratocarcinoma stem cells [66]. In this study, the rate of intracellular protease leakage into the cell medium was directly proportional to the cytotoxicity of PtNPs and RA against SH-SY5Y cells.…”

Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer

“…HDAC inhibitors are well known as anticancer agents by inhibiting cell viability and inducing apoptosis in a variety of cancer cells. Combination of an HDAC inhibitor such as trichostatin A with GO-Ag NPs induced DNA fragmentation and double-strand breaks and eventually induced apoptosis, all at higher levels than did a single treatment in human ovarian cancer cells [ 191 ].…”