Anticancer effect of S‑allyl‑L‑cysteine via induction of apoptosis in human bladder cancer cells

Abstract

Abstract.To exa m i ne the anticancer effects of S-allyl-L-cysteine (SAC) in human bladder cancer cells and to identify possible molecular mechanisms, bladder cancer cell lines (HTB5, HTB9, JON, UMUC14, T24, and cisplatin resistant-T24R2) were incubated with SAC, and cell proliferaproliferation was measured using the Cell Counting Kit-8 assay and clonogenic assay. Cell cycle and apoptosis were evaluated by flow cytometry. Expression levels of apoptosis-and cell cycle-associated proteins were analyzed by western blotting. Proliferation and colony formation in bladder cancer cells was significantly inhibited by SAC treatment in a dose-dependent manner. SAC treatment significantly enhanced apoptosis and promoted a cell cycle arrest in the S phase. SAC also increased the expression of apoptosis-related genes, including caspases, poly (ADP-ribose) polymerase and cytochrome c. SAC had an anticancer effect on bladder cancer cells in vitro, at least partially, through the induction of apoptosis and a cell cycle arrest. SAC is a potential therapeutic agent for the treatment of bladder cancer. IntroductionUrinary bladder cancer is a common malignancy of the urinary tract and responsible for 150,000 deaths annually. Urinary bladder cancer is the seventh most prevalent type of cancer worldwide (1). In Korea, the number of cases of urinary bladder cancer increased from 2,180 in 1999 to 3,549 in 2011 (2). The incidence of urinary bladder cancer is four times higher in men compared with women (3).Cisplatin-based combination chemotherapy is widely used against advanced and metastatic bladder cancer. Such drugs, however, yield poor oncological outcomes and show high toxicity (4), and there is growing interest in other types of therapeutic agents for the treatment of advanced bladder cancer (4). The development of more effective and less toxic therapeutic regimens is vital for the improvement of survival among patients with bladder cancer.Recent studies showed that natural bioactive compounds, including isothiocyanate and amygdalin, have anticancer effects on bladder cancer cells (5,6). Garlic, a species of the Allium genus, has been utilized for medicinal purposes in recorded history (7-9). Organosulfur compounds from Allium vegetables have been reported to have possible preventive and therapeutic properties against some types of cancer (7). Sulfur-containing compounds in garlic can be broadly categorized as oil-soluble (diallylsulphide, diallyldisulphide and diallyltrisulfide) or water-soluble [S-allyl-L-cysteine (SAC)] (8). SAC is the most abundant organosulfur compound in aged-garlic extract and was reported to have antioxidant, and neuroprotective properties as well as anticancer activity (9-11). Several studies showed that SAC has anticancer effects by suppressing the cellular proliferation and metastasis and induces apoptosis in a number of cancer models, including ovarian, prostate and hepatocellular carcinoma (7-9). Nevertheless, whether SAC has anticancer effects in bladder cancer remains an open question.In the present...

S‐Allyl cysteine in garlic (Allium sativum): Formation, biofunction, and resistance to food processing for value‐added product development

“…The results were supported by those of the study by Ho et al. (2018), which showed that SAC promoted S‐phase inactivation and apoptosis of A2780 ovarian cancer cells, which is associated with the downregulation of Bcl‐2 and the upregulation of Bax and caspase‐3. SAC induced apoptosis in T24 and T24R2 bladder cancer cells, inhibiting the proliferation of these cells, altering the expression of apoptosis and cell cycle markers, and disrupting the cell cycle.…”

“…Garlic can also help reduce blood pressure. One of the most intriguing properties of garlic is its anticancer activity; notably, it is used to prevent stomach and colon cancers (Ho et al., 2018). Platelet aggregation and hyperlipidemia have also been shown to be reduced by garlic (Rahman, 2007).…”

Effects of different processing methods on the antioxidant and immune stimulating abilities of garlic

“…However, the most widely used processing method for removing the unpleasant odor and taste of garlic is heat treatment (García-Villalón et al, 2016). During heat treatment, various physicochemical changes occur, including changes in odor, nutrient content, flavor and color.An important compound, S-Allylcysteine, is produced in large amounts during the aging process of garlic and is a key compound responsible for the multiple pharmacological activities of garlic such as antioxidant, anticancer, and neurotrophic activities (Baluchnejadmojarad, Kiasalari, Afshin-Majd, Ghasemi, & Roghani, 2017;Ho et al, 2018). S-Allylcysteine is formed by the enzymatic hydrolysis of γ-glutamyl-S-allyl cysteine (GSAC) by γ-glutamyl transpeptidase (γ-GTP) (Kodera et al, 2002).…”

Aged garlic extract and its constituent, S‑allyl‑L‑cysteine, induce the apoptosis of neuroblastoma cancer cells due to mitochondrial membrane depolarization

“…Among the natural compound, garlic, a species of the Allium genus, has been used throughout recorded history for both culinary and medicinal purposes (20,21,24). In our previous study, as well as in numerous other reports, it was observed that AGE induced a decrease in the viability of several human cancer cell lines (1,20,24,41). This result represents an interesting finding, since in conventional cancer chemotherapy, numerous issues hamper successful treatment.…”