Sulforaphane potentiates oxaliplatin-induced cell growth inhibition in colorectal cancer cells via induction of different modes of cell death

Abstract

The objective of this study was to investigate, whether the plant-derived isothiocyanate Sulforaphane (SFN) enhances the anti-tumor activities of the chemotherapeutic agent oxaliplatin (Ox) in a cell culture model of colorectal cancer. Caco-2 and SW-620 cells were cultured under standard conditions and treated with increasing concentrations of SFN [1-20µM] and/or Ox [100nM-10µM]. For co-incubation, cells were pre-treated with SFN for 24 h. Cell growth was determined by BrdU incorporation. Drug interactions were assessed using the combination-index method (CI) (Cl<1 indicates synergism). Apoptotic events were characterized by different ELISA techniques. Protein levels were examined by Western blot analysis. Annexin-V-and propidium-iodide (PI)-staining followed by FACS analysis was 2 used to differentiate between apoptotic and necrotic events. SFN and Ox alone inhibited cell growth of Caco-2-and SW620-cells in a dose dependent manner, an effect, which could be synergistically enhanced, when cells were incubated with the combination o f both agents.Cotreated cells further displayed distinctive morphological changes that occurred during the apoptotic process, such as cell surface exposure of phosphatidylserine, membrane blebbing as well as the occurence of cytoplasmic histone-associated DNA fragments. Further observations thereby pointed towards simultaneous activation of both extrinsic and intrinsic apoptotic pathways. With increasing concentrations and treatment duration a shift from apoptotic to necrotic cell death could be observed. In conclusion, the data suggest that the isothiocyanate SFN sensitizes colon cancer cells to Ox-induced cell growth inhibition via induction of different modes of cell

Sulforaphane‑induced epigenetic regulation of Nrf2 expression by DNA methyltransferase in human Caco‑2 cells

“…In addition, sulforaphane inhibited the initiation of carcinogen-induced skin tumours (18,19), and reduced metastatic spread of melanoma in mice (20). This chemical also promoted the antiproliferative activity of other antiproliferative agents, including oxaliplatin (21).…”

Effects of β-carotene on Expression of Selected MicroRNAs, Histone Acetylation, and DNA Methylation in Colon Cancer Stem Cells

“…Dietary factors can also regulate histone modification. For example, sulforaphane from broccoli, cauliflower, and cabbage have been reported to exert anti-cancer effects on pancreatic, prostate, and CRCs by targeting HDAC [27,28].…”

Phenethyl isothiocyanate synergistically induces apoptosis with Gefitinib in non–small cell lung cancer cells via endoplasmic reticulum stress‐mediated degradation of Mcl‐1

“…36 Among all the antiapoptotic Bcl-2 family members, Mcl-1 functions as a major survival factor, particularly in solid cancers, 37,38 and has emerged as a potential and promising target for cancer therapy. 39 Kang et al 40 Studies had discovered that PEITC was able to enhance the cytotoxic effects with other chemotherapeutic drugs, 43 including platinum, 20,44 paclitaxel, 25,26 gemcitabine, 45,46 and etoposide. 47 However, the synergistic effect of PEITC and EGFR-TKI Gefitinib in The ER is the entrance site for newly synthesized polypeptides of membrane and secreted proteins and is a central intracellular organelle in the secretory pathway.…”