Abstract B042: Anticancer effects of processed garlic constituent diallyl trisulfide on head and neck squamous cell carcinoma

Abstract

Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Despite significant advances in therapeutic approaches, survival rate is less than 50%. Early detection and treatment will help in prevention of spreading of invasive cancer and thereby improve the survival rates. Studies showed that dietary intake of Allium vegetables lowered the risk of various cancers. Studies reported DATS as a promising chemopreventive constituent of processed garlic that induced cell cycle arrest and apoptosis in prostate and breast cancer. However, it has not been investigated for its efficacy and molecular mechanisms of chemopreventive effects of DATS against HNSCC. Herein, we investigated the effect of DATS on HNSCC FaDu, D562, UMSCC-22A, UMSCC-22B, and Cal33 cells in culture. DATS (10-100 µM) treatment significantly reduced the growth, proliferation, and survival of HNSCC cells. We observed that DATS treatments significantly induced G2/M cell cycle arrest. DATS treatment resulted in the accumulation of cyclin B1 and induced the levels of cip1/p21. DATS-induced mitotic arrest was attenuated by NAC pretreatment, which suggested that DATS mediates growth-suppressive effects by induction of ROS. DATS induced cell death through apoptosis, which was associated with ROS production. Further, DATS increased the ratio of Bax/Bcl2 and cleavage of caspase-3 and PARP and decreased the levels of XIAP. Exposure of HNSCC cells to pharmacologic concentrations of DATS (1-10 μM) resulted in inhibition of cancer stem cells (CSC) fraction as evidenced by CD133high/CD44high fraction of cells, aldehyde dehydrogenase 1 (ALDH1) activity, and spheroid formation. DATS-treated tumor xenograft also revealed its in vivo inhibitory effect on CSCs. We observed for the first time that DATS treatment decreased tumor incidence and inhibited tumor promotion and progression in 4-Nitroquinoline 1-oxide (4-NQO)-induced mouse oral carcinogenesis model. Taken together, DATS strongly inhibited cell proliferation, induced cell cycle arrest, cell death via apoptosis, mitochondrial dysfunction and ROS generation and reduced CSC fraction, and decreased tumor incidence, promotion, and progression in 4-NQO model. Citation Format: Sivapar Mathan, Shivendra Singh, Rana P. Singh. Anticancer effects of processed garlic constituent diallyl trisulfide on head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B042.