No abstract

Colorectal cancer is the third most lethal and fourth most commonly diagnosed cancer worldwide. Sinapic acid, a derivative of hydroxycinnamic acid, is a promising phytochemical exhibiting numerous pharmacological activities in various systems. It is a substantial chain-breaking antioxidant that operates as a radical scavenger. The aim of this research was to investigate the antiproliferative effect of sinapic acid on the HT-29 cell line, besides the mechanisms underlying this activity. The effect of sinapic acid on the viability of HT-29 cell line was investigated using XTT assay. the levels of BCL-2, cleaved caspase 3, BAX, cleaved PARP and 8-oxo-dG were measured using ELISA. Gamma-H2AX and cytochrome C expression was assessed semi-quantitatively using immunofluorescence staining. Sinapic acid at 200 μM and higher doses produced a significant antiproliferative effect on HT-29 cells. The IC50 value was found to be 317.5 μM for 24 hours. Sinapic acid (317.5 μM) significantly elevated cleaved caspase 3, BAX, cleaved PARP and 8-oxo-dG levels. the levels of γ-H2AX foci are significantly higher while the levels of cytochrome-C are lower in sinapic acid treated HT-29 cells. These results indicate that sinapic acid has an antiproliferative, apoptotic and genotoxic effect on colon cancer cells.

Background. Sorafenib is a multikinase inhibitor currently used in the treatment of hepatocellular carcinoma, renal cell carcinoma and thyroid cancer.Objectives. The literature on this agent is scarce. This study aimed to evaluate the effects of sorafenib when administered to both healthy and cisplatin-induced rats.Materials and methods. The animals were divided into 4 groups: 1) control group that received 0.9% saline intraperitoneally (C); 2) group administered a single dose (7 mg/kg) of cisplatin (Cis); 3) a group administered 20 mg/kg of sorafenib for 7 days (Sor); 4) group administered 20 mg/kg of sorafenib followed by 7 mg/kg of cisplatin for 7 days (Cis+Sor). All animals were sacrificed 7 days after the completion of their treatment arm, and serum and tissue samples were taken. Results.Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and interleukin 38 (IL-38) levels were increased in the Sor and Cis+Sor groups compared to the control group. When compared with the control group, serum urea, creatinine, kidney IL-1β, and tumor necrosis factor alpha (TNF-α) levels did not change in the Sor group. When compared to the Cis group, the levels of these parameters decreased in the Cis+Sor group. Conclusions.According to the data obtained, sorafenib caused liver toxicity when given to both healthy and cisplatin-induced rats. While sorafenib did not cause any significant changes in the kidneys when given to healthy rats, it had a healing effect in kidneys after stress induced by cisplatin.

Objective:The objective of the present study was to evaluate the effects of Rhodiola rosea in the indomethacin-induced ulcer model in rats and to clarify the underlying mechanisms of action.Methods: Rats in treatment groups were treated with Rhodiola rosea (RR) 14 days. Peptic ulcer was induced by indomethacin (IND) injection (100 mg/kg, p.o.). The groups (n = 6) were designed as; Group I (control); Group II (IND): After 24h of food starvation, rats were given only 100 mg/kg IND by oral gavage to induce gastric mucosal injury. Group III (ESO): Rats were pretreated with 20 mg/kg of ESO for 14 consecutive days by oral gavage. Group IV (RR): Rats were pretreated with 500 mg/kg RR for 14 consecutive days with oral gavage.Results: Rhodiola rosea effectively alleviated indomethacin-induced ulcer via reduction in oxidative stress (decreased MDA and increased SOD, and GSH). Moreover, Rhodiola rosea alleviated indomethacin-induced damage by regulating expressions of COX enzymes, prostaglandin E2, proliferating cell nuclear antigen (PCNA), cell proliferation, apoptosis and regulated the NF-κB signaling pathway. Rhodiola rosea also attenuated inflammatory injury by suppressing TNF-𝛼𝛼, IL-1β, and NF-κB. The caspase-3 expression was also down-regulated in stomach tissues. Conclusions:In conclusion, Rhodiola rosea protected the gastric mucosa from harmful effects of indomethacin and as a natural medicinal herb, Rhodiola rosea might be a potential therapeutic agent for preventing and treating indomethacininduced gastric damage.

BackgroundGambogic acid has demonstrated inhibitory effects on the growth of various cancer cell types, such as breast cancer, pancreatic cancer, prostate cancer, lung cancer, and osteosarcoma. This study aims to investigate the antiproliferative activity of Gambogic acid on SNU-16 cells derived from gastric signet ring cell carcinoma and elucidate the underlying mechanisms. Material and MethodsThe cytotoxic effect of gambogic acid was evaluated in SNU-16 cells by treating them with different concentrations of the compound, and the XTT cell viability assay was employed to assess cell viability.ELISA was used to measure bax, BCL-2, caspase 3, PARP, and 8-oxo-dG levels. Additionally, immuno uorescence staining was applied to assess 8-oxo-dG and LC3β levels in SNU-16 cells. ResultsIt was observed that gambogic acid exerted a dose-dependent and statistically signi cant antiproliferative effect on SNU-16 cells. The IC 50 value of gambogic acid in SNU-16 cells was found to be 655.1 nM for 24 hours. Subsequent investigations conducted using the IC 50 dose revealed a signi cant upregulation of apoptotic proteins including cleaved caspase 3, Bax, and cleaved PARP (p < 0.001), along with a downregulation of BCL-2 (p < 0.001), an anti-apoptotic protein. Moreover, the administration of this drug led to an upregulation of 8-oxo-dG (p < 0.001), a widely acknowledged biomarker indicating oxidative damage in DNA, as well as an increase in LC3β levels (p < 0.05), a marker associated with autophagy. ConclusionThe antiproliferative effect of gambogic acid against gastric signet ring cell carcinoma is attributed to its ability to induce apoptosis and autophagy. This discovery highlights the promising potential of gambogic acid as a treatment option for gastric signet ring cell carcinoma.