Inhibition of cancer cell proliferation and apoptosis-inducing activity of fungal taxol and its precursor baccatin III purified from endophytic Fusarium solani

Cancer Cell International

Chelliah Jayabaskaran¹  Anjali A Karande¹  Gini C Kuriakose¹  Ramanathan Sujay¹  Balabhadrapatruni VSK Chakravarthi² 

[1] Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India;Present Address: Department of Pathology, University of Michigan, Ann Arbor 48109-0602, MI, USA

关键词: Mitochondria;    Jurkat;    Caspase;    Anticancer;    Endophyte;    Apoptosis;    Baccatin III;    Taxol;   

Others  :  792729
DOI  :  10.1186/1475-2867-13-105

 received in 2013-05-04, accepted in 2013-09-27,  发布年份 2013

【 摘 要 】

Background

Taxol (generic name paclitaxel), a plant-derived antineoplastic agent, used widely against breast, ovarian and lung cancer, was originally isolated from the bark of the Pacific yew, Taxus brevifolia. The limited supply of the drug has prompted efforts to find alternative sources, such as chemical synthesis, tissue and cell cultures of the Taxus species both of which are expensive and yield low levels. Fermentation processes with microorganisms would be the methods of choice to lower the costs and increase yields. Previously we have reported that F. solani isolated from T. celebica produced taxol and its precursor baccatin III in liquid grown cultures J Biosci 33:259-67, 2008. This study was performed to evaluate the inhibition of proliferation and induction of apoptosis of cancer cell lines by the fungal taxol and fungal baccatin III of F. solani isolated from T. celebica.

Methods

Cell lines such as HeLa, HepG2, Jurkat, Ovcar3 and T47D were cultured individually and treated with fungal taxol, baccatin III with or without caspase inhibitors according to experimental requirements. Their efficacy on apoptotic induction was examined.

Results

Both fungal taxol and baccatin III inhibited cell proliferation of a number of cancer cell lines with IC₅₀ ranging from 0.005 to 0.2 μM for fungal taxol and 2 to 5 μM for fungal baccatin III. They also induced apoptosis in JR4-Jurkat cells with a possible involvement of anti-apoptotic Bcl2 and loss in mitochondrial membrane potential, and was unaffected by inhibitors of caspase-9,-2 or -3 but was prevented in presence of caspase-10 inhibitor. DNA fragmentation was also observed in cells treated with fungal taxol and baccatin III.

Conclusions

The cytotoxic activity exhibited by fungal taxol and baccatin III involves the same mechanism, dependent on caspase-10 and membrane potential loss of mitochondria, with taxol having far greater cytotoxic potential.

【 授权许可】

   
2013 Chakravarthi et al.; licensee BioMed Central Ltd.

【 图 表 】

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