首页|Biological Screening and Radiolabeling of Raptinal as a Potential Anticancer Novel Drug in Hepatocellular Carcinoma Model
Biological Screening and Radiolabeling of Raptinal as a Potential Anticancer Novel Drug in Hepatocellular Carcinoma Model
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NSTL
Elsevier
New synthetic compound Raptinal (RAP) was investigated on different biological levels for its potential anticancer activity. RAP showed higher antiproliferative activity on HepG2 cell line with IC50 0.62 mu M compared to MCF-7 and HCT-116 (4.03 and 92.3 mu M) respectively. Moreover, RAP induces early stage of apoptosis in the most sensitive HepG2 treated cells after 24 hr with cell cycle arrest in both sub G(0)-G(1) and G(0)-G(1) phases and minimal cell count in G(2)/M mitotic phase with apoptotic index 9.25-fold higher than to control. RAP induces overexpression of key apoptotic genes such as Fas receptor, Caspase-8, Caspase-9, Bax and P53. Western blotting confirm the observation on protein level via over-expression of Caspase-9, Cytochrome-C and higher ration of Bax/Bcl-2. In addition, RAP was radiolabeled using one of the most important diagnostic radioactive isotopes, technetium-99m (Tc-99m), with a radiochemical yield of 92.7 +/- 0.41 %. Quality control and biological distribution of Tc-99m-RAP in both healthy and HCC rat model were investigated. Biodistribution profile revealed the localization of RAP in liver tissues (20.5 +/- 2.6 %) of HCC models at half an hour post intravenous injection. Histopathological examination confirmed the biodistribution of RAP into liver tissue with induction of karyomegaly in the nuclei of hepatocytes as well as others that proceeded into apoptosis. Molecular docking suggested RAP binds in binding pocket of p53 cancer mutant Y220C making reactivation of the mutant form which is a promising strategy for further investigation on molecular level as a novel anticancer therapeutics. All the results support the use of RAP as a potential anticancer drug in HCC and its Tc-99m complex as an imaging probe.
NSTL
Elsevier
