Effect of allyl isothiocyanate on the viability and apoptosis of the human cervical cancer HeLa cell line in vitro

Qin,Guangyi; Li,Ping; Xue,Zhuowei

doi:10.3892/ol.2018.8428

Effect of allyl isothiocyanate on the viability and apoptosis of the human cervical cancer HeLa cell line in vitro

Authors:
- Guangyi Qin
- Ping Li
- Zhuowei Xue
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Affiliations: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
Published online on: April 4, 2018 https://doi.org/10.3892/ol.2018.8428
Pages: 8756-8760

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Abstract

The present study aimed to investigate the effect of allyl isothiocyanate (AITC) on the viability and apoptosis of the human cervical cancer HeLa cell line in vitro, and to explore the potential underlying mechanisms of this. HeLa cells were treated with varying concentrations of AITC for different durations. The cell viability was then measured using a Cell Counting kit‑8 assay and the apoptosis rate of the cells was detected using flow cytometry. Additionally, the B cell lymphoma‑2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax) mRNA expression levels were determined by reverse transcription‑quantitative polymerase chain reaction, while the Bax and Bcl‑2 protein expression levels in cells were detected by western blot analysis. AITC was revealed to inhibit the viability of HeLa cells. AITC was revealed to induce the apoptosis of HeLa cells, as the apoptosis rate increased gradually with an increase in the dose. As the concentration of AITC increased, the Bax mRNA expression level increased, whilst the Bcl‑2 mRNA expression level decreased. Furthermore, the Bax protein expression intensity increased whilst Bcl‑2 protein expression intensity decreased, thereby resulting in a decrease in the ratio of Bcl‑2/Bax proteins. AITC may inhibit cell viability by inducing the apoptosis of HeLa cells and this may be accounted for by the imbalance in the Bcl‑2/Bax expression ratio.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
2	Xu K and Thornalley PJ: Studies on the mechanism of the inhibition of human leukaemia cell growth by dietary isothiocyanates and their cysteine adducts in vitro. Biochem Pharmacol. 60:221–231. 2000. View Article : Google Scholar : PubMed/NCBI
3	Bhattacharya A, Li Y, Wade KL, Paonessa JD, Fahey JW and Zhang Y: Allyl isothiocyanate-rich mustard seed powder inhibits bladder cancer growth and muscle invasion. Carcinogenesis. 31:2105–2110. 2010. View Article : Google Scholar : PubMed/NCBI
4	Geng F, Tang L, Li Y, Yang L, Choi KS, Kazim AL and Zhang Y: Allyl isothiocyanate arrests cancer cells in mitosis, and mitotic arrest in turn leads to apoptosis via Bcl-2 protein phosphorylation. J Biol Chem. 286:32259–32267. 2011. View Article : Google Scholar : PubMed/NCBI
5	Xiao D, Srivastava SK, Lew KL, Zeng Y, Hershberger P, Johnson CS, Trump DL and Singh SV: Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits proliferation of human prostate cancer cells by causing G2/M arrest and inducing apoptosis. Carcinogenesis. 24:891–897. 2003. View Article : Google Scholar : PubMed/NCBI
6	Wu CL, Huang AC, Yang JS, Liao CL, Lu HF, Chou ST, Ma CY, Hsia TC, Ko YC and Chung JG: Benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC)-mediated generation of reactive oxygen species causes cell cycle arrest and induces apoptosis via activation of caspase-3, mitochondria dysfunction and nitric oxide (NO) in human osteogenic sarcoma U-2 OS cells. J Orthop Res. 29:1199–1209. 2011. View Article : Google Scholar : PubMed/NCBI
7	Bo P, Lien JC, Chen YY, Yu FS, Lu HF, Yu CS, Chou YC, Yu CC and Chung JG: Allyl isothiocyanate induces cell toxicity by multiple pathways in human breast cancer cells. Am J Chin Med. 44:415–437. 2016. View Article : Google Scholar : PubMed/NCBI
8	Sávio AL, da Silva GN and Salvadori DM: Inhibition of bladder cancer cell proliferation by allyl isothiocyanate (mustard essential oil). Mutat Res. 771:29–35. 2015. View Article : Google Scholar : PubMed/NCBI
9	Bhattacharya A, Li Y, Geng F, Munday R and Zhang Y: The principal urinary metabolite of allyl isothiocyanate, N-acetyl-S-(N-allylthiocarbamoyl) cysteine, inhibits the growth and muscle invasion of bladder cancer. Carcinogenesis. 33:394–398. 2012. View Article : Google Scholar : PubMed/NCBI
10	Savio AL, da Silva GN, de Camargo EA and Salvadori DM: Cell cycle kinetics, apoptosis rates, DNA damage and TP53 gene expression in bladder cancer cells treated with allyl isothiocyanate (mustard essential oil). Mutat Res. 762:40–46. 2014. View Article : Google Scholar : PubMed/NCBI
11	Tripathi K, Hussein UK, Anupalli R, Barnett R, Bachaboina L, Scalici J, Rocconi RP, Owen LB, Piazza GA and Palle K: Allyl isothiocyanate induces replication-associated DNA damage response in NSCLC cells and sensitizes to ionizing radiation. Oncotarget. 6:5237–5252. 2015. View Article : Google Scholar : PubMed/NCBI
12	Lau WS, Chen T and Wong YS: Allyl isothiocyanate induces G2/M arrest in human colorectal adenocarcinoma SW620 cells through down-regulation of Cdc25B and Cdc25C. Mol Med Rep. 3:1023–1030. 2010.PubMed/NCBI
13	Lai KC, Lu CC, Tang YJ, Chiang JH, Kuo DH, Chen FA, Chen IL and Yang JS: Allyl isothiocyanate inhibits cell metastasis through suppression of the MAPK pathways in epidermal growth factor-stimulated HT29 human colorectal adenocarcinoma cells. Oncol Rep. 31:189–196. 2014. View Article : Google Scholar : PubMed/NCBI
14	Hwang ES and Kim GH: Allyl isothiocyanate influences cell adhesion, migration and metalloproteinase gene expression in SK-Hep1 cells. Exp Biol Med (Maywood). 234:105–111. 2009. View Article : Google Scholar : PubMed/NCBI
15	Garcia A, Haza AI, Arranz N, Rafter J and Morales P: Protective effects of isothiocyanates alone or in combination with vitamin C towards N-nitrosodibutylamine or N-nitrosopiperidine-induced oxidative DNA damage in the single-cell gel electrophoresis (SCGE)/HepG2 assay. J ApplToxicol. 28:196–204. 2008.
16	Xu C, Shen G, Yuan X, Kim JH, Gopalkrishnan A, Keum YS, Nair S and Kong AN: ERK and JNK signaling pathways are involved in the regulation of activator protein 1 and cell death elicited by three isothiocyanates in human prostate cancer PC-3 cells. Carcinogenesis. 27:437–445. 2006. View Article : Google Scholar : PubMed/NCBI
17	Tang L, Zirpoli GR, Guru K, Moysich KB, Zhang Y, Ambrosone CB and McCann SE: Intake of cruciferous vegetables modifies bladder cancer survival. Cancer Epidemiol Biomarkers Prev. 19:1806–1811. 2010. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
19	Louhivuori LM, Bart G, Larsson KP, Louhivuori V, Näsman J, Nordström T, Koivisto AP and Akerman KE: Differentiation dependent expression of TRPA1 and TRPM8 channels in IMR-32 human neuroblastoma cells. J Cell Physiol. 221:67–74. 2009. View Article : Google Scholar : PubMed/NCBI
20	Chen NG, Chen KT, Lu CC, Lan YH, Lai CH, Chung YT, Yang JS and Lin YC: Allyl isothiocyanate triggers G2/M phase arrest and apoptosis in human brain malignant glioma GBM 8401 cells through a mitochondria-dependent pathway. Oncol Rep. 24:449–455. 2010.PubMed/NCBI
21	Zhu Y, Zhuang JX, Wang Q, Zhang HY and Yang P: Inhibitory effect of benzyl isothiocyanate on proliferation in vitro of human glioma cells. Asian Pac J Cancer Prev. 14:2607–2610. 2013. View Article : Google Scholar : PubMed/NCBI
22	Gupta P, Kim B, Kim SH and Srivastava SK: Molecular targets of isothiocyanates in cancer: Recent advances. Mol Nutr Food Res. 58:1685–1707. 2014. View Article : Google Scholar : PubMed/NCBI
23	Hasegawa T, Nishino H and Iwashima A: Isothiocyanates inhibit cell cycle progression of HeLa cells at G2/M phase. Anticancer Drugs. 4:273–279. 1993. View Article : Google Scholar : PubMed/NCBI
24	Cory S and Adams JM: The Bcl2 family: Regulators of the cellular life-or-death switch. Nat Rev Cancer. 2:647–656. 2002. View Article : Google Scholar : PubMed/NCBI
25	Oltvai ZN, Milliman CL and Korsmeyer SJ: Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 74:609–619. 1993. View Article : Google Scholar : PubMed/NCBI