Combined treatment with silver graphene quantum dot, radiation, and 17‐AAG induces anticancer effects in breast cancer cells

Abstract

We aimed to investigate the possible anticancer effects of radiation in combination with 17‐allylamino‐17‐demethoxy geldanamycin (17‐AAG) and silver graphene quantum dot (SQD) in breast cancer (BC) cells. MCF‐7 BC cells treated with, or without, different concentrations of 17‐AAG and synthesized SQD and cellular viability detected. The growth inhibitory effects of low concentrations of 17‐AAG with minimally toxic concentration of SQD in combination with 2 Gy of X‐ray radiation were examined. The apoptosis induction assessed by acridine orange/ethedium bromide staining. Likewise, the levels of lactate, hydrogen peroxide (H2O2), nitric oxide (NO) were evaluated. The relative gene expression levels of Bax and Bcl‐2 were detected by real‐time polymerase chain reaction and the Bax/Bcl‐2 expression ratio was determined. Moreover, the protein expression of epidermal growth factor receptor (EGFR) was assessed by western blot analysis. Treatment with low concentrations of 17‐AAG and SQD at a minimally toxic concentration promoted inhibition of BC cell growth and induced apoptosis. In addition, significant reduction in cell viability was seen in triple combination versus all double and single treatments. Indeed 17‐AAG and SQD in combined with radiation significantly increased the H2O2 and NO versus single and double treated cases. In addition, triple combination treatment showed decreased lactate level in compared tomonotherapies. EGFR protein expression levels were found to decreased in all double and triple combined cases versus single treatments. Additionally, in double and triple treatments, Bax/Bcl2 ratio were higher in compared to single treatments. Treatment with low concentrations of 17‐AAG and SQD at a minimally toxic concentration tends to induce anticancer effects and increase the radiation effects when applied with 2 Gy of radiation versus radiation monotherapy.

Effects of Radiotherapy in Combination With Irinotecan and 17-AAG on Bcl-2 and Caspase 3 Gene Expression in Colorectal Cancer Cells

“…21 (17 allyl amino)-17demethoxygeldanamycin (17-AAG) is a heat shock protein 90 (HSP90) inhibitor, which exerts anti-tumor effects and induces apoptosis in cancer cells. 21,22 In addition, in preclinical models, it exerts anticancer activity in different cancer types. [22][23][24] The combination of chemotherapy and radiation therapy in other studies increased the treatment efficiency.…”

“…21,22 In addition, in preclinical models, it exerts anticancer activity in different cancer types. [22][23][24] The combination of chemotherapy and radiation therapy in other studies increased the treatment efficiency. 22,25 Chemoradiotherapy prevents tumor proliferation.…”

Cytotoxic and Radiosensitizing Effects of Folic Acid-Conjugated Gold Nanoparticles and Doxorubicin on Colorectal Cancer Cells

“…35 Also in a similar study, when silver nanoparticles (in minimal cytotoxic concentration) combined with a chemotherapeutic agent and 2Gy of x-Ray irradiation could increase the level of H2O2 as an oxidative stress marker and induce apoptosis in the breast cancer cell line. 36 In the present study for describing one of the possible underlying mechanisms of cytotoxicity of the triple combination treatment, the MDA level was measured. According to the results, the triple combination treatment with significant cytotoxic effects increased the MDA generation level.…”

A Preliminary in vitro and in vivo Evaluation of the Effect and Action Mechanism of 17-AAG Combined With Azoles Against Azole-Resistant Candida spp.

“…When compared with geldanamycin, 17-AAG exhibited a higher stability, better bioavailability, and greater water solubility ( Li et al, 2020b ), which allows its wider distribution across animal tissues, thereby signifying its greater potential in clinical applications. Recent studies have demonstrated that low concentration of 17-AAG can inhibit the growth of breast cancer cells, induce apoptosis ( Esgandari et al, 2021 ), and prevent myocardial dysfunction after myocardial infarction in rats ( Marunouchi et al, 2021 ). HSP90 is a host-dependent factor of human coronaviruses MERS-CoV SARS-COV and SARS-COV-2, while HSP90 inhibitors can be used as an effective broad-spectrum antiviral agent against human coronaviruses ( Li et al, 2020a ).…”