Cytotoxic effect of synthetic stilbenes against breast, colon and lung cancer cell lines / Kathleen J. Jalani.

• Auteur principal: J. Jalani, Kathleen
• Format: Thèse
• Langue: anglais
• Publié: 2012
• Sujets: RC0254 Neoplasms. Tumors. Oncology (including Cancer); Cancer
• Accès en ligne: https://ir.uitm.edu.my/id/eprint/54183/1/54183.pdf

The struggle to fight and find a cure for cancer has been discussed and researched widely. The rise in cancers incidents has also caused an increase in economic burden. Various methods to treat cancer have been developed but one of the most efficient ways is through chemotherapy. The source of chemotherapy drugs includes natural products and synthetic compounds. Nevertheless, advanced technology has made synthetic drugs more attractive as compared to natural products. In the present study, 12 synthetic stilbenes (SI - S12) were investigated for their potential as anticancer drugs. These stilbenes were tested for cytotoxicity against the human breast (MDA231, MDA468 and T47D), colon (HCT116 and HT29) and lung (A549) cancer cell lines and non-cancerous (WRL68, MRC-5 and FHC) cell lines. From the cytotoxic test, eight active stilbenes (SI, S2, S3, S4, S6, S8, S9 and Sll) with IC50 ≤10 µM were identified. For further studies, their selectivity towards cancer and noncancerous cell lines were also determined. Apoptosis was then investigated using; Cell Death Detection ELISAPLUS (Roche kit) in 72 hour and for flowcytometry using Annexin V with Propidium iodide (PI) at four different time points (12 h, 24 h, 48 h and 72 h). The Cell Death Assay and Flowcytometry results showed that all the active stilbenes kill cancer cells mostly through apoptosis. All stilbenes were optimized synthetically in Heck reaction, where the percentages of increased yields were noted. From the eight active stilbenes, only three stilbenes (S2, S8 & Sll) were produced in higher yield compared to a previous study. In vivo acute toxicity studies and all the active stilbenes was conducted using balb/c mice. No significant difference in body weight and food intake changes in both female and male mice was observed. The high dose was 200 mg/kg and low dose was 100 mg/kg. For histology, the mice's organs of liver, spleen, heart, colon, kidney and lung were observed. All mice survived from the doses except for group S3HD, S6LD, S6HD, SllLD and SllLD had showed toxicity where mild lesion can be seen inside the histology of spleen and lung but still considered normal, therefore all active stilbenes were safe in doses up to 200 mg/kg.