Metabolism reprogramming has been linked with the initiation, metastasis, and recurrence of cancer. The aldehyde dehydrogenase (ALDH) family is the most important enzyme system for aldehyde metabolism. The human ALDH family is composed of 19 members. ALDH1A3 participates in various physiological processes in human cells by oxidizing all-trans-retinal to retinoic acid. ALDH1A3 expression is regulated by many factors, and it is associated with the development, progression, and prognosis of cancers. In addition, ALDH1A3 influences a diverse range of biological characteristics within cancer stem cells and can act as a marker for these cells. Thus, growing evidence indicates that ALDH1A3 has the potential to be used as a target for cancer diagnosis and therapy.

N-Carbamylglutamate (NCG), an effective precursor of arginine (ARG), can enhance ARG synthesis, increase intestinal growth, and improve reproductive performance. However, the antioxidant effect of NCG remains largely unknown. This study aims to survey the effects of ARG and NCG supplementation on the antioxidant statuses of the liver and plasma in rats under oxidative stress. Rats were fed for 30 days with one of the three iso-nitrogenous diets: basal diet (BD), BD plus 1% ARG, and BD plus 0.1% NCG. On day 28, half of the rats fed with BD were intraperitoneally injected with 12 mg per kg body weight of diquat (diquat group) and the other half was injected intraperitoneally with sterile 0.9% NaCl solution (control group). The other diet groups also received an intraperitoneal injection of 12 mg per kg body weight of diquat, as follows: diquat + 1% ARG (DT + ARG), and diquat + 0.1% NCG (DT + NCG). Rat liver and plasma samples obtained 48 h after diquat injection were analyzed. Results indicated that diquat significantly affected the plasma conventional biochemical components (relative to the controls), which were partially alleviated in both the DT + ARG and DT + NCG groups (P < 0.05). Diquat also significantly decreased the glutathione (GSH) content (by 30.0%), and decreased anti-superoxide anion (ASA; by 13.8%) and anti-hydroxyl radical (AHR; by 38.9%) abilities in the plasma, and also decreased catalase (CAT) activity both in the liver (by 17.5%) and plasma (by 33.4%) compared with the control group. By contrast, diquat increased the malondialdehyde (MDA) content (by 23.0%) in the plasma (P < 0.05) compared with the control group. Relative to those of the diquat group, higher CAT activity and GSH content were noted in the plasma of the DT + ARG group and in the liver of both DT + ARG and DT + NCG groups (P < 0.05). Furthermore, the DT + ARG group exhibited significantly enhanced plasma ASA activity (P < 0.05). The DT + NCG group showed significantly improved total antioxidant capacity (T-AOC) in the liver and plasma (P < 0.05). Increased GSH content and elevated ASA and AHR activities were also found, but the MDA content in the plasma was depleted (P < 0.05). Compared with the DT + ARG group, the DT + NCG group showed increased liver and plasma T-AOC, enhanced plasma AHR activity, increased liver ASA activity, and decreased plasma MDA content (P < 0.05). Overall, supplementation of 1% ARG and 0.1% NCG can partially protect the liver and plasma from oxidative stress. Furthermore, compared with 1% ARG, 0.1% NCG more effectively alleviated oxidative stress.

Diallyl trisulfide (DATS), a garlic organosulfide, has shown excellent chemopreventive potential. Cisplatin (DDP) is widely used to treat solid malignant tumors, but causing serious side effects. In the current study, we attempted to elucidate the chemopreventive mechanisms of DATS in human gastric cancer BGC-823 cells in vitro, and to investigate whether DATS could enhance the anti-tumor efficacy of DDP and improve quality of life in BGC-823 xenograft mice in vivo. Treatment with DATS (25-400 μmol/L) dose-dependently inhibited the viability of BGC-823 cells in vitro with an IC of 115.2±4.3 μmol/L after 24 h drug exposure. DATS (50-200 μmol/L) induced cell cycle arrest at G/M phase in BGC-823 cells, which correlated with significant accumulation of cyclin A2 and B1. DATS also induced BGC-823 cell apoptosis, which was accompanied by the modulation of Bcl-2 family members and caspase cascade activation. In BGC-823 xenograft mice, administration of DATS (20-40 mg·kg·d, ip) dose-dependently inhibited tumor growth and markedly reduced the number of Ki-67 positive cells in tumors. Interestingly, combined administration of DATS (30 mg·kg·d, ip) with DDP (5 mg/kg, every 5 d, ip) exhibited enhanced anti-tumor activity with fewer side effects. We showed that treatment of BGC-823 cells with DATS in vitro and in vivo significantly activated kinases such as p38 and JNK/MAPK and attenuated the Nrf2/Akt pathway. This study provides evidence that DATS exerts anticancer effects and enhances the antitumor efficacy of DDP, making it a novel candidate for adjuvant therapy for gastric cancer.