Chan, Zachariah Chee Ken and Leong, Kok Hoong and Kareem, Huda Salah and Norazit, Anwar and Noor, Suzita Mohd and Ariffin, Azhar (2020) Activation of death receptor, DR5 and mitochondria-mediated apoptosis by a 3,4,5-trimethoxybenzyloxy derivative in wild-type and p53 mutant colorectal cancer cell lines. Naunyn-Schmiedebergs Archives of Pharmacology, 393 (3). pp. 405-417. ISSN 0028-1298, DOI https://doi.org/10.1007/s00210-019-01730-2.
Full text not available from this repository.Abstract
The rationale of designing compounds containing a (3,4,5-trimethoxybenzyloxy) phenyl moiety is largely due to its potential antioxidant and cytotoxic activities. A previous study focused on its antioxidant mechanism, whereas in this study, we investigated the cytotoxicity of a series of 28 analogues and the mechanism of apoptosis of the most cytotoxic compound against wild-type (HCT-116) and p53 mutant (HT-29) colorectal cancer cell lines. The series of analogues comprise of different families, namely hydrazone, oxadiazole, thiosemicarbazides and triazoles. In the initial cytotoxicity screening, N-(3,4,5-trimethoxybenzylidene)-4-(3,4,5-trimethoxybenzyloxy) benzohydrazide, henceforth known as, P5H, was found to be most cytotoxic against human colorectal cancer cell lines (IC50 for HCT-116=11.79 mu M and HT-29=18.52 mu M). Additionally, P5H was found to have some degree of selectivity towards cancer cells compared to normal human colon cells (CCD-112 CoN). Subsequent investigation had brought insight on P5H ability to induce apoptosis in both HCT-116 and HT-29 cell lines. Cell cycle analysis showed both cell lines were arrested at the G2/M phase upon treatment. Our study concluded that P5H induced the death receptor, DR5 in HCT-116 and mitochondria-mediated apoptosis pathway in HT-29. Therefore, P5H may be a promising candidate as a chemotherapy agent against colon cancer.
| Item Type: | Article |
|---|---|
| Funders: | Universiti Malaya (RP021-14AFR), Universiti Malaya (RP035-17AFR), Ministry of Education, Malaysia (FP024-2014A) |
| Uncontrolled Keywords: | Apoptosis; Colorectal cancer; Trimethoxybenzyloxy; HCT-116; HT-29; p53 |
| Subjects: | Q Science > QD Chemistry R Medicine > R Medicine (General) R Medicine > RS Pharmacy and materia medica |
| Divisions: | Faculty of Medicine Faculty of Science > Department of Chemistry Faculty of Pharmacy |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 02 Dec 2022 07:28 |
| Last Modified: | 02 Dec 2022 07:29 |
| URI: | http://eprints.um.edu.my/id/eprint/38157 |
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