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Nanoparticulate Quillaja saponin induces apoptosis in human leukemia cell lines with a high therapeutic index.

Hu K, Berenjian S, Larsson R, Gullbo J, Nygren P, Lövgren T, Morein B - Int J Nanomedicine (2010)

Bottom Line: The toxic effect was abolished by converting QS fractions into stable nanoparticles through the binding of QS to cholesterol.The nontoxic BBE blocked the cell killing effect of KGI in a concentration-dependent manner.In conclusion, the formulation of QS into nanoparticles has the potential of becoming a new class of anticancer agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Sciences, Section of Virology, Uppsala University, Uppsala, Sweden.

ABSTRACT
Saponin fractions of Quillaja saponaria Molina (QS) have cytotoxic activity against cancer cells in vitro, but are too toxic to be useful in the clinic. The toxic effect was abolished by converting QS fractions into stable nanoparticles through the binding of QS to cholesterol. Two fractions of QS were selected for particle formation, one with an acyl-chain (ASAP) was used to form killing and growth-inhibiting (KGI) particles, and the other without the acyl-chain (DSAP) was used to formulate blocking and balancing effect (BBE) particles. KGI showed significant growth inhibiting and cancer cell-killing activities in nine of 10 cell lines while BBE showed that on one cell line. The monoblastoid lymphoma cell line U937 was selected for analyzing the mode of action. Low concentrations of KGI (0.5 and 2 microg/mL) induced irreversible exit from the cell cycle, differentiation measured by cytokine production, and eventually programmed cell death (apoptosis). Compared to normal human monocytes, the U937 cells were 30-fold more sensitive to KGI. The nontoxic BBE blocked the cell killing effect of KGI in a concentration-dependent manner. In conclusion, the formulation of QS into nanoparticles has the potential of becoming a new class of anticancer agents.

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The synergistic effect of KGI and BBE with other anticancer drugs on U937 cells A) KGI (10 μg/mL) exerts a strong synergistic effect with Docetaxel (0.0016 μM) and B) BBE (10 μg/mL) with Fludarabine (2 μM).
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f6-ijn-5-051: The synergistic effect of KGI and BBE with other anticancer drugs on U937 cells A) KGI (10 μg/mL) exerts a strong synergistic effect with Docetaxel (0.0016 μM) and B) BBE (10 μg/mL) with Fludarabine (2 μM).

Mentions: The cytotoxic effect of KGI and BBE was tested in several leukemia cell lines using the FMCA and Alamar Blue assays (Table 2). The results demonstrated that several other leukemic cell lines showed high sensitivity to KGI including the vincristine resistant subline U937-Vcr, acute lymphocytic leukemia CEM cells and acute myelocytic leukemia Mv-411 and THP-1 cells. In contrast, acute lymphocytic leukemia Jurkat- and etoposide-resistant CEM/R cells as well as the myeloma 8226 cell lines were less sensitive. None of the cell lines tested, apart from U937-Vcr, was sensitive to BBE. Moreover, as seen in Figure 6, KGI and BBE exert strong synergistic effects with docetaxel and fludarabine on U937 cells, respectively.


Nanoparticulate Quillaja saponin induces apoptosis in human leukemia cell lines with a high therapeutic index.

Hu K, Berenjian S, Larsson R, Gullbo J, Nygren P, Lövgren T, Morein B - Int J Nanomedicine (2010)

The synergistic effect of KGI and BBE with other anticancer drugs on U937 cells A) KGI (10 μg/mL) exerts a strong synergistic effect with Docetaxel (0.0016 μM) and B) BBE (10 μg/mL) with Fludarabine (2 μM).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2819906&req=5

f6-ijn-5-051: The synergistic effect of KGI and BBE with other anticancer drugs on U937 cells A) KGI (10 μg/mL) exerts a strong synergistic effect with Docetaxel (0.0016 μM) and B) BBE (10 μg/mL) with Fludarabine (2 μM).
Mentions: The cytotoxic effect of KGI and BBE was tested in several leukemia cell lines using the FMCA and Alamar Blue assays (Table 2). The results demonstrated that several other leukemic cell lines showed high sensitivity to KGI including the vincristine resistant subline U937-Vcr, acute lymphocytic leukemia CEM cells and acute myelocytic leukemia Mv-411 and THP-1 cells. In contrast, acute lymphocytic leukemia Jurkat- and etoposide-resistant CEM/R cells as well as the myeloma 8226 cell lines were less sensitive. None of the cell lines tested, apart from U937-Vcr, was sensitive to BBE. Moreover, as seen in Figure 6, KGI and BBE exert strong synergistic effects with docetaxel and fludarabine on U937 cells, respectively.

Bottom Line: The toxic effect was abolished by converting QS fractions into stable nanoparticles through the binding of QS to cholesterol.The nontoxic BBE blocked the cell killing effect of KGI in a concentration-dependent manner.In conclusion, the formulation of QS into nanoparticles has the potential of becoming a new class of anticancer agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Sciences, Section of Virology, Uppsala University, Uppsala, Sweden.

ABSTRACT
Saponin fractions of Quillaja saponaria Molina (QS) have cytotoxic activity against cancer cells in vitro, but are too toxic to be useful in the clinic. The toxic effect was abolished by converting QS fractions into stable nanoparticles through the binding of QS to cholesterol. Two fractions of QS were selected for particle formation, one with an acyl-chain (ASAP) was used to form killing and growth-inhibiting (KGI) particles, and the other without the acyl-chain (DSAP) was used to formulate blocking and balancing effect (BBE) particles. KGI showed significant growth inhibiting and cancer cell-killing activities in nine of 10 cell lines while BBE showed that on one cell line. The monoblastoid lymphoma cell line U937 was selected for analyzing the mode of action. Low concentrations of KGI (0.5 and 2 microg/mL) induced irreversible exit from the cell cycle, differentiation measured by cytokine production, and eventually programmed cell death (apoptosis). Compared to normal human monocytes, the U937 cells were 30-fold more sensitive to KGI. The nontoxic BBE blocked the cell killing effect of KGI in a concentration-dependent manner. In conclusion, the formulation of QS into nanoparticles has the potential of becoming a new class of anticancer agents.

Show MeSH
Related in: MedlinePlus