Phenethyl isothiocyanate potentiates anti‐tumour effect of doxorubicin through Akt‐dependent pathway

Abstract

The present study aims to investigate the in vivo and in vitro anti-tumour properties of phenethyl isothiocyanate (PEITC) alone and in combination with doxorubicin (Dox). The anti-tumour activity was evaluated in vitro by MTT assay using cultured human breast cancer cell line (MCF-7) and human hepatoma cell line (HepG-2) cell lines. In vivo, Ehrlich solid tumour model was used. Tumour volume, weight and antioxidant parameters were determined. Immunohistochemistry analysis for active (cleaved) caspase-3 was also performed. We tested the effect of PEITC treatment on pAkt/Akt ratio, NF-κB p65 DNA binding activity and caspase-9 enzyme activity in both MCF-7 and HepG-2 cell lines. Effect of PEITC treatment on cell migration was assessed by wound healing assay. PEITC and/or Dox treatment significantly inhibited solid tumour volume and tumour weight when compared with control mice. PEITC treatment significantly reduced oxidative stress caused by Dox treatment as indicated by significant increase in total antioxidant capacity and decrease in malondialdehyde level. Microscopic examination of tumour tissues showed a significant increase in active (cleaved) caspase-3 expression in PEITC and/or Dox treated groups. PEITC showed a dose-dependent inhibition of MCF-7 and HepG-2 cellular viability. PEITC inhibited Akt and NF-κB activation and increased caspase-9 activity in a dose-dependent manner. PEITC treatment effectively inhibited both MCF-7 and HepG-2 cell migration. We can conclude that PEITC acts via multiple molecular targets to elicit anti-carcinogenic activity. PEITC/Dox combination therapy might be a potential novel strategy, which may benefit patients with breast and liver cancers.

Extracellular cholesterol oxidase production by Streptomyces aegyptia, in vitro anticancer activities against rhabdomyosarcoma, breast cancer cell-lines and in vivo apoptosis

“…Tumor volumes were measured from the fifth day of tumor induction and before the beginning of the treatment (day 0) and were carried out every five days for a period of 20 days. “Volume of solid tumor was monitored by vernier caliper and was calculated using the following formula: V = (L × S 2 ) × 0.5 65 , where (L) is the longest diameter of tumor and (S) is its shortest perpendicular diameter. Anti-tumor effectiveness was evaluated by the estimation of the average change of tumor volume in the treatment group (ΔT) and the average change of tumor volume in the control EAC bearing mice (ΔC).…”

Metabolic targets of watercress and PEITC in MCF-7 and MCF-10A cells explain differential sensitisation responses to ionising radiation

“…It causes cell cycle arrest and mitochondrial damage in a wide variety of cell lines and it is a potent inducer of apoptosis [13–16]. Combined treatment of cancer cells with PEITC and established chemotherapeutic agents such as cisplatin and doxorubicin potentiates their cancer-killing properties [17, 18]. These findings support the potential of PEITC to be used as an adjuvant treatment during radiotherapy in cancer patients.…”

Irisin Enhances Doxorubicin-Induced Cell Apoptosis in Pancreatic Cancer by Inhibiting the PI3K/AKT/NF-κB Pathway

“…Chemoresistance of DOX is a complex process involving the regulation of many cellular biology processes through various mechanisms, including increased expression of p-glycoprotein efflux transporter protein [7, 8]. Many studies have suggested that inhibition of the PI3K/AKT and NF-κB pathways plays an important role in improving the effectiveness of DOX [9,10]. The PI3K/AKT pathway plays a crucial role in cell proliferation, survival, and drug resistance through regulating multiple downstream cascades in various cancers, including PC cells [11,12].…”

“…The PI3K/AKT pathway plays a crucial role in cell proliferation, survival, and drug resistance through regulating multiple downstream cascades in various cancers, including PC cells [11,12]. Once activated, AKT can phosphorylate multiple substrates and downstream effectors, such as the mammalian target of rapamycin (mTOR) family, caspases, cell cycle proteins, and NF-κB [9]. NF-κB also has a therapeutic effect in ameliorating chemoresistance [13,14].…”