Allyl isothiocyanate triggers G2/M phase arrest and apoptosis in human brain malignant glioma GBM 8401 cells through a mitochondria-dependent pathway

Abstract

Abstract. Isothiocyanates (ITCs) are present as glucosinolates in various cruciferous vegetables. Allyl isothiocyanate (AITC) is one of the common naturally occurring isothiocyanates. Recent studies have shown that AITC significantly inhibited survival of leukemia HL-60, bladder cancer UM-UC-3 and colon cancer HT-29 cells in vitro. In this study, we demonstrate that AITC significantly decreased proliferation and viability of human brain malignant glioma GBM 8401 cells in a dose-dependent manner with IC 50 9.25±0.69 μM for 24 h-treatment. The analysis of cell cycle distribution also showed that AITC induced significantly G2/M arrest and sub-G1 phase (apoptotic population) in GBM 8401 cells. AITC markedly reduced the CDK1/cyclin B activity and protein levels by CDK1 activity assay and Western blot analysis. AITC-induced apoptotic cell death and this evidence was confirmed by morphological assessment and DAPI staining. Pretreatment with specific inhibitors of caspase-3 (Z-DEVE-FMK) and -9 (Z-LEHD-FMK) significantly reduced caspase-3 and -9 activity in GBM 8401 cells. Western blot analysis and colorimetric assays also displayed that AITC caused a time-dependent increase in cytosolic cytochrome c, pro-caspase-9, Apaf-1, AIF, Endo G and the stimulated caspase-9 and -3 activity. Our results suggest that AITC is a potent anti-human brain malignant glioma drug and it shows a remarkable action on cell cycle arrest before commitment for apoptosis is reached.

Allyl Isothiocyanate Suppresses the Proliferation in Oral Squamous Cell Carcinoma via Mediating the KDM8/CCNA1 Axis

“…The results showed a similarity with a previous study [20]. Previously conducted studies have indicated that allyl isothiocyanate (AITC) can prompt G2/M cell cycle arrest in various types of cancer, such as brain glioma, colorectal adenocarcinoma, and breast adenocarcinoma [40,58,59]. CCNA1, which is a member of the highly conserved cyclin family, may be involved in regulating the cell cycle at both G1/S and G2/M transition points [6].…”

“…By inhibiting HDAC activity, AITC can increase histone acetylation, alter gene expression, and prevent cancer cell growth [34]. Furthermore, AITC has been shown to induce apoptosis and G2/M phase arrest in human brain malignant glioma GBM 8401 cells [40] as well as apoptotic death in human cisplatin-resistant oral cancer cells [29]. Various preclinical studies have shown that AITC can inhibit lung, breast, gastric, prostate, and bladder cancer, but this does not reflect in the pilot trials performed in humans to date [41][42][43].…”

Allyl isothiocyanate suppressed the proliferation of oral squamous cell carcinoma in vitro, in vivo, and in patient-derived tumor xenografts by downregulating the KDM8/CCNA1 axis

“…Previously conducted studies have indicated that allyl isothiocyanate (AITC) can prompt G2/M cell cycle arrest in various types of cancer, such as brain glioma, colorectal adenocarcinoma, and breast adenocarcinoma [34,48,49]. CCNA1, which is a member of the highly conserved cyclin family, may be involved in regulating the cell cycle at both G1/S and G2/M transition points [20].…”

“…By inhibiting HDAC activity, AITC can increase histone acetylation, alter gene expression, and prevent cancer cell growth [28]. Furthermore, AITC has been shown to induce apoptosis and G2/M phase arrest in human brain malignant glioma GBM 8401 cells [34] as well as apoptotic death in human cisplatin-resistant oral cancer cells [23]. While AITC has been found to repress tumor cell proliferation in various cancer cell lines, including brain, lung, breast, colorectal, bladder, and cervical cancer cell lines [35][36][37], there is limited research addressing the AITC-mediated effects on OSCC.…”