Anti-cancer effects of chemotherapeutic agent; 17-AAG, in combined with gold nanoparticles and irradiation in human colorectal cancer cells

Abstract

Objective The present study evaluated the anti-cancer effects of irradiation (Ir) alone, Ir after heat shock protein 90 inhibitor; 17allylamino-17-demethoxygeldanamycin (17-AAG) and gold nanoparticle (GNP) treatments in human colorectal cancer cell line (HCT-116), with the targeting of related mechanisms. Methods Water-soluble tetrazolium salt-1 assay was utilized to study the cytotoxic effects of 17-AAG, GNP, Ir in single and combination cases on the cell viability of HCT-116 cells. The cells were examined with DNA fragmentation electrophoresis and evaluated for apoptosis induction. Caspase-3 expression as a critical apoptosis element in protein level was detected by western blotting.Results Treatment with 17-AAG in a dose dependent manner for 24 h inhibited the cellular viability of HCT-116 cells. GNP at a dose of 70 μM had the lowest cytotoxic effects and was thus selected for combination treatment studies. Based on the results, GNP at a dose of 70 μM did not have a significant effect on cellular viability of HCT-116. In contrast, the evaluation of double and triple combinations, GNP with Ir (2 Gy of 6 MV X-ray radiation) and 17-AAG in double combinations induced significant cytotoxicity. Both DNA damage pattern and caspase-3 protein upregulation were present in Ir,GNP/17-AAG,GNP and Ir,17-AAG combinations compared to single treatments. Furthermore, in the three combination of GNP,Ir,17-AAG, radiosensitization effects (increased caspase-3 expression) occurred with a minimum concentration of 17-AAG. Conclusion According to the results of this study, 17-AAG as chemotherapeutic agent in combination with Ir and GNP exerts noticeable anti-cancer effects, inhibited cell viability, and increased apoptosis occurrence by upregulating caspase-3 expression. It is suggested that these combinations should be more evaluated as a promising candidate for colorectal cancer treatment.

Dihydropyrimidine Dehydrogenase Levels in Colorectal Cancer Cells Treated with a Combination of Heat Shock Protein 90 Inhibitor and Oxaliplatin or Capecitabine

“…So, it is important to improve the treatment outcome by assessing cancer response. 17,35,36 DPD is an important enzyme in the biochemical functions of the antimetabolite drugs whose altered expression is related to adverse events following fluoropyrimidine- and oxaliplatin-based treatments. 24,25 In two panels of CRC cell lines, double chemotherapy with capecitabine, oxaliplatin, and 17-AAG was superior to single chemotherapy in terms of efficacy.…”

The Rational Design and Biological Mechanisms of Nanoradiosensitizers

“…17-allylamino-17-demethoxygeldanamycin (17-AAG) is an inhibitor of HSP90 that induces the apoptosis of cancer cells. The combined treatment of 17-AAG, GNPs and irradiation induced the highest expression of caspase-3 in HCT-116 cells compared with single treatments or combinations of two treatments [146]. Cisplatin-loaded gold nanoparticles (Au@PAH-Pt/DMMA, 78 nm) aggregated rapidly through electrostatic interactions in the acidic tumor microenvironment.…”

Regulatory Effects of Apatinib in Combination with Piperine on MDM-2 Gene Expression, Glutathione Peroxidase Activity and Nitric Oxide level as Mechanisms of Cytotoxicity in Colorectal Cancer Cells

“…Colorectal cancer (CRC) is the third-largest cancer world width 1,2 and is related to a high rate of mortality. [1][2][3][4][5] Recently, clinical studies have been interested in detecting novel integrating targeted treatments and combination chemotherapy regimens. 2 Combination chemotherapy comes into importance in CRC treatment but drug resistance is inevitable.…”