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

Chakravarthi BV, Sujay R, Kuriakose GC, Karande AA, Jayabaskaran C - Cancer Cell Int. (2013)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India. cjb@biochem.iisc.ernet.in.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Fungal taxol and baccatin III exhibit concentration- and time-dependent apoptosis in JR4-Jurkat cells. Cells (0.25 × 106) were treated with fungal taxol (A) or baccatin III (B) at indicated concentrations for 48 h. A time-course experiment of fungal taxol- and baccatin III-induced apoptosis (C). Other details are as described in legend to Figure 1. The percentage of apoptotic cells (sub G1 peak) was calculated on the basis of respective histograms.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4016216&req=5

Figure 2: Fungal taxol and baccatin III exhibit concentration- and time-dependent apoptosis in JR4-Jurkat cells. Cells (0.25 × 106) were treated with fungal taxol (A) or baccatin III (B) at indicated concentrations for 48 h. A time-course experiment of fungal taxol- and baccatin III-induced apoptosis (C). Other details are as described in legend to Figure 1. The percentage of apoptotic cells (sub G1 peak) was calculated on the basis of respective histograms.

Mentions: We observed a clear dose- and time- dependent induction of apoptosis by taxol and baccatin III in cells. The maximal increase in the frequency of apoptotic cells was observed after 48 h of incubation with 0.1 μM fungal taxol (68%) (Figure 2A and 2C), while the maximal induction of apoptosis by fungal baccatin III was obtained in 48 h at a concentration of 5 μM (65%) (Figure 2B and 2C).


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

Chakravarthi BV, Sujay R, Kuriakose GC, Karande AA, Jayabaskaran C - Cancer Cell Int. (2013)

Fungal taxol and baccatin III exhibit concentration- and time-dependent apoptosis in JR4-Jurkat cells. Cells (0.25 × 106) were treated with fungal taxol (A) or baccatin III (B) at indicated concentrations for 48 h. A time-course experiment of fungal taxol- and baccatin III-induced apoptosis (C). Other details are as described in legend to Figure 1. The percentage of apoptotic cells (sub G1 peak) was calculated on the basis of respective histograms.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016216&req=5

Figure 2: Fungal taxol and baccatin III exhibit concentration- and time-dependent apoptosis in JR4-Jurkat cells. Cells (0.25 × 106) were treated with fungal taxol (A) or baccatin III (B) at indicated concentrations for 48 h. A time-course experiment of fungal taxol- and baccatin III-induced apoptosis (C). Other details are as described in legend to Figure 1. The percentage of apoptotic cells (sub G1 peak) was calculated on the basis of respective histograms.
Mentions: We observed a clear dose- and time- dependent induction of apoptosis by taxol and baccatin III in cells. The maximal increase in the frequency of apoptotic cells was observed after 48 h of incubation with 0.1 μM fungal taxol (68%) (Figure 2A and 2C), while the maximal induction of apoptosis by fungal baccatin III was obtained in 48 h at a concentration of 5 μM (65%) (Figure 2B and 2C).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India. cjb@biochem.iisc.ernet.in.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus