Benzyl isothiocyanate sensitizes human pancreatic cancer cells to radiation by inducing apoptosis

Abstract

Abstract.Isothiocyanates are a class of naturally occurring chemopreventive agents known to suppress proliferation of cancer cells in culture. The present study was undertaken in order to examine the effects of benzyl isothiocyanate (BITC), one of the common dietary isothiocyanates, on the radiosensitivity of human pancreatic cancer cells and to gain insights into the underlying molecular mechanism of BITC-induced radiosensitization. Two human pancreatic cancer cell lines, PANC-1 and MIAPaCa-2, were treated with BITC and irradiated with X-rays. Radiation sensitivity, apoptosis, and protein levels were determined by a clonogenic assay, fluorescence microscopic analysis with DAPI staining and Western blotting, respectively. MIAPaCa-2 cells were relatively more sensitive to BITC treatment compared with PANC-1 cells. Radiosensitization was observed in both PANC-1 and MIAPaCa-2 cells incubated with BITC at 5 to 10 µM and 2.5 to 5 µM for 24 h, respectively. The combination treatments with BITC and X-rays also revealed an increased percentage of apoptotic cells. In addition, treatment with BITC and X-rays resulted in a decrease in the protein levels of the X-linked inhibitor of apoptosis (XIAP), inhibitor of apoptosis (IAP) family protein, and in a marked increase in the apoptosis protease activating factor-1 (Apaf-1), essential for activation of caspase-9 in stress-induced apoptosis. BITC may be a useful radiosensitizer for radiotherapy of pancreatic cancers.

Combination treatment of resveratrol and capsaicin radiosensitizes pancreatic tumor cells by unbalancing DNA repair response to radiotherapy towards cell death

“…In fact, RT treatment alone led to significant increase in BCL2 levels (Figure 5, p<0.01), 13 and a trend to diminish BAX levels. Irradiated Mia PaCa-2 cells also changed their BAX to BCL2 balance in the same way (20), the control of BCL2 family member levels being known as a mechanism of RT resistance (29). Our result suggests that addition of BFCs to irradiation counteracts this resistance mechanism.…”

“…Several BFCs radiosensitize tumor cells such as the polyphenols curcumin (18) and quercetin (19) or the sulfamide sulforaphane (20), for example. Considering our previous work on pancreatic tumor cell chemosensitization by combination of capsaicin and resveratrol (9), we tested the same approach with radiotherapy.…”

Evaluation of the radiosensitizing potency of bromelain for radiation therapy of 4T1 breast cancer cells

“…In various reports have shown that radiation-induced apoptosis is enhanced by some agents such as apigenin, curcumin, genistein, sulforaphane, benzyl isothiocyanate, olaparib, rucaparib, elesclomol, 17-DMA, LY2603618, MK87776, and AZD1775, EphB4, human PLK1. [2327293233] Our observations are opposite of their results. However, in many studies such as Rafehi et al .,[34] clonogenic formation assay was introduced as the gold standard to investigate radiosensitizers.…”

Mutations in the FHA-domain of ectopically expressed NBS1 lead to radiosensitization and to no increase in somatic mutation rates via a partial suppression of homologous recombination

“…Many radiosensitizers that function at a cellular level have already been investigated. These include apoptosis-enhancing natural chemical components [1], chemicals which increase DNA damage resulting from radiation [2, 3], kinase inhibitors for ATM/ATR/Chk1/Chk2 [3], and PARP inhibitors [3], although these agents are not tumor tissue-specific sensitizers.…”