Evaluation of the anticancer activity of enzymatically synthesized Baccatin III: an intermediate precursor of Taxol®

评估酶合成的 Baccatin III(紫杉醇® 的中间体前体)的抗癌活性

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作者:Balendra Sah, Madhuree Kumari, Kamalraj Subban, Jayabaskaran Chelliah

Abstract

Baccatin III is an important precursor for the synthesis of clinically important anticancer drug Taxol. Previously, we have characterized a key enzyme of 10-deacetylbaccatin III-10-β-O-acetyltransferase (DBAT) which catalyses the 10-deacetylbaccatin III into baccatin III in taxol biosynthesis. Here, in the present study, we have evaluated and compared the cytotoxic properties of the enzymatically synthesized baccatin III (ESB III) with standard baccatin III in different human cancer cell lines, namely human cervical cancer (HeLa), human lung cancer (A549), human skin cancer (A431) and human liver cancer cells (HepG2). Among the various cancer lines tested, HeLa was more susceptible to ESB III with IC50 of 4.30 µM while IC50 values for A549, A431 and HepG2 ranged from 4 to 7.81 µM. Further, it showed G2/M phase cell cycle arrest, production of reactive oxygen species and depolarised mitochondrial membrane potential. In addition, annexin V-FITC staining was performed which showed the apoptotic cell death of HeLa cells, when treated with ESB III. Hence, ESB III was capable to show anticancer activities by inducing apoptotic cell death which could further be used for the semisynthesis of taxol in future.

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