Targeting Heat Shock Proteins by Phenethyl Isothiocyanate Results in Cell-Cycle Arrest and Apoptosis of Human Breast Cancer Cells

Abstract

Heat shock proteins (HSPs) are chaperones for several client proteins involved in transcriptional regulation, signal transduction, and cell cycle control. HSPs (27, 70, and 90) are abundantly expressed in a wide range of cancers and are transcriptionally regulated by heat shock factor (HSF1). Most of the synthetic HSP inhibitors exhibit toxicity, therefore, searching for inhibitors with limited or no toxicity will be of help. The objective of the present study was to determine the effect of natural isothiocyanate (phenethyl isothiocyanate; PEITC) on different HSPs (27, 70, and 90) and HSF1 in 2 breast cancer cell lines, namely breast adenocarcinoma MCF-7 (with wild type p53) and highly metastatic breast cancer cell MDA-MB-231 (with mutated p53). PEITC significantly inhibited the expression of HSPs (particularly HSP 90) and HSF1. Molecular consequences due to HSP inhibition were downregulation of cell-cycle regulatory proteins like Cyclin B1, CDK1, Cdc25C, PLK-1, and upregulation of p21 irrespective of p53 status. These modulations were accompanied by cell-cycle arrest at G2/M phase and apoptosis by activation of caspases 3 and 9. PEITC therefore may be regarded as a potent HSP inhibitor and an antitumor agent in the treatment of breast cancer.

Phenethyl isothiocyanate inhibits growth of human chronic myeloid leukemia K562 cells via reactive oxygen species generation and caspases

“…PEITC is a potential cancer chemopreventive constituent of edible cruciferous vegetables and has been shown to inhibit various models of cancer, including prostate, breast, ovarian, oral and lung cancer (3)(4)(5)(6)(7). The present study aimed to characterize the anti-leukemia effects of PEITC.…”

“…Phenethyl isothiocyanate (PEITC) is an important compound obtained from cruciferous vegetables that is effective in numerous types of cancer, including prostate, breast, ovarian, oral and lung cancer (3)(4)(5)(6)(7). Several mechanisms, including the inhibition of cytochrome p450 enzymes, the induction of phase II detoxification enzymes (8) and the activation of death receptors 4 and 5 (9), are involved in the anti-tumor effects of PEITC.…”

Phytonutrients from Fruits and Vegetables in Breast Cancer Control

“…These effects were accompanied by cell-cycle arrest at G2/M phase and apoptosis by activation of caspases 3 and 9. 35 The chemopreventive activity of blueberries was studied by Yee et al 22 in triple-negative breast cancer cell lines. It was revealed that the phytochemicals present in blueberries decreased proliferation of HCC38, HCC1937, and MDA-MB-231 cells.…”

Heat Shock Proteins and Cancer: Plant Based Therapy

“…Boesenbergin A treatment is caused significantly suppressing of HSP70 in human T4-lymphoblastoid cells [36]. Phenethyl isothiocyanate (PEITC), a natural compound found in some plants, significantly reduced HSP27, HSP70, HSP90 and HSF-1 expressions in MCF-7 and MDA-MB-231 breast cancer cell lines [134]. Triptolide from Triptergium wilfordii suppressed HSP70 expression via inhibiting heat shock response in HeLa cells [141].…”