Apoptosis induction by sulfur‐containing compounds in malignant and nonmalignant human cells

Abstract

Plants have traditionally represented a main source for the discovery of many biologically active substances with therapeutic values. Sulfur-containing compounds exhibit pleiotropic biological effects supporting their potential use in multitargeted cancer prevention and treatment. As potential anti-cancer agents, they have been shown to inhibit or retard the growth of various cancer cells in culture and implanted tumors in vivo. The compounds significantly inhibit experimental tumorigenesis in a wide range of animal models. A critical and well-elucidated cellular mechanism involved in the anticancer activities of sulfur-containing compounds is the induction of apoptosis through the fine-tuning of orchestrated intracellular signal transduction. This review summarizes the established proapoptotic activities of sulfur-containing compounds in malignant and nonmalignant cells with a special focus on their molecular mechanisms. The potential toxicological implications of proapoptotic effects on normal cells will also be discussed.

Anticancer Mechanism of Sulfur-Containing Compounds

“…As revealed by several studies, DAS, DADS, DATS, and ajoene reduced viability of human malignant cells (neuroblastoma cells, prostate cancer cells, lung tumor cells, and leukemia cells) without affecting viability of human normal cells (human primary neurons, normal prostate epithelia cells, normal lung fibroblasts, and healthy mononuclear blood cells) [115][116][117][118]. Both BITC and AITC support this evidence, showing inhibition of breast cancer cell survival and minimal effects on healthy breast cell survival [1].…”

“…Furthermore, ITCs are able to oxidize a member of the Trx-dependent antioxidant system, namely peroxiredoxin (Prx), which exists in mammalian cells in six different forms at least. PEITC (15 μM) and SFN (60 μM) rapidly and selectively oxidize the mitochondrial Prx3, but not the cytosolic Prx1 and Prx2, which are not oxidized under the same conditions [1,101]. Increased levels of ROS are reported after SFN treatment (5-20 μM) of p53-null MG63 osteosarcoma cells [104] and PEITC and BITC treatment of U-2 OS cells (10 μM and 7.5 μM, respectively) [100].…”

“…4). As for Allium compounds, p53 seems to be an unnecessary participant in the apoptotic pathway induced by ITCs and this gives evidence of their potential use for tumors with a p53 mutation [1].…”

“…Sulforaphane (SFN) from broccoli, erucin contained in rocket, phenethyl isothiocyanate (PEITC) in watercress, allyl isothiocyanate (AITC) in cabbage are frequently studied as cancer chemopreventive agents. Chemopreventive efficacy of ITCs was reported in various studies and imputable to different mechanisms, including inhibition of proliferation through the induction of cell-cycle arrest and apoptosis, modulation of hormone receptor expression, antiangiogenic and antimetastasis potential, induction of autophagy, and induction of xenobiotic-metabolizing enzymes [1].…”

Induction of the mitochondria-mediated apoptosis in human esophageal cancer cells by DS2, a newly synthetic diterpenoid analog, is regulated by Bax and caused by generation of reactive oxygen species

“…We were intrigued by Jaridonin's anticancer profile to make use of its special scaffold as an introductory template to synthesize novel Jaridonin derivatives to develop effective and safe anticancer agents. Numerous studies have identified sulfur-containing compounds possess multiple biological effects supporting their potential use in multi-targeted cancer prevention and treatment [20]. And recently, expeditious synthetic methods that were based on the Jaridonin scaffold were successfully built by our group to access a series of disulfide bond-substituted derivatives with improved anticancer activity, among them, DS2 (the synthesis and the structure identification of DS2 are shown in Supplementary Figures S1, S2 and S3) suggesting that disulfide bond-substituted modifications seem to be tolerated for producing biologically interesting molecules.…”