Biological Screening of Novel Derivatives of Valproic Acid for Anticancer and Antiangiogenic Properties

مقال فى مجلة

2015

Background: Valproic acid (VPA) is a potent anticancer and antiangiogenic agent. However, design and
synthesis of chemical derivatives with improved antiangiogenic and anticancer activities are still necessary. In
this study a library of novel derivatives of VPA was synthesized and tested. Methods: A human liver cancer cell
line (HepG2) and a human normal embryonic kidney cell line (HEK 293) were exposed to various concentrations
of VPA derivatives for 24 hours and cell viability was checked by MTT colorimetric assay. Anti-angiogenic
properties were evaluated in transgenic zebrafish embryos. Results: N-valproylglycine derivatives suppressed
survival almost 70% (p value 0.001) in HepG2 cells but only 10-12% in HEK 293 cells (p value 0.133). They
also suppressed angiogenic blood vessel formation by 80% when used between 2-20 μM in zebrafish embryos.
Valproic acid hydrazides showed moderate level of anticancer activity by affecting 30-50% (p value 0.001) of cell
viability in HepG2 cells and 8-10% in HEK293 cells (p value 0.034). Conclusion: The majority of compounds in
this study showed potent and stronger antiangiogenic and anticancer activity than VPA. They proved selectively
toxic to cancer cells and safer for normal cells. Moreover, these compounds inhibited developmental angiogenesis
in zebrafish embryos. Based on the fact that liver is a highly vascularized organ, in case of liver carcinoma these
compounds have the potential to target the pathological angiogenesis and could be an effective strategy to treat
hepatocellular carcinoma.

• رقم الانشاء: 15 (18),
• مجلة/صحيفة: Asian Pac J Cancer Prev,
• الصفحات: 7785-7792