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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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Related in: MedlinePlus

Free non-particulate ASAP causes early cell destruction but not the particulate form. A) Cell destruction measured by hemolytic effect. KGI and BBE are virtually non-lytic while free ASAP is highly lytic. B) Free ASAP induces early cell death in human normal monocytes like in cancer cells, but not the ASAP formulated into KGI particles measured by Trypan Blue staining. C) Free ASAP induces early cell death in U937 tumor cells within minutes at the concentrations indicated. KGI does not induce this rapid cell death. D) Cell membrane destruction measured by the release of the intracellular enzyme thymidine kinase (TK) to the extracellular medium. Free ASAP causes TK release, while KGI does not cause the leakage. E) Free ASAP causes cell necrosis but not KGI particles.
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f2-ijn-5-051: Free non-particulate ASAP causes early cell destruction but not the particulate form. A) Cell destruction measured by hemolytic effect. KGI and BBE are virtually non-lytic while free ASAP is highly lytic. B) Free ASAP induces early cell death in human normal monocytes like in cancer cells, but not the ASAP formulated into KGI particles measured by Trypan Blue staining. C) Free ASAP induces early cell death in U937 tumor cells within minutes at the concentrations indicated. KGI does not induce this rapid cell death. D) Cell membrane destruction measured by the release of the intracellular enzyme thymidine kinase (TK) to the extracellular medium. Free ASAP causes TK release, while KGI does not cause the leakage. E) Free ASAP causes cell necrosis but not KGI particles.

Mentions: The cell membrane lytic effect of the ASAP and DSAP or their particulate forms the KGI and BBE was measured on RBCs. Free ASAP lysed RBCs at a concentration of 5 μg/mL (Figure 2a) whereas the KGI particles induced RBC lysis at a 20-fold higher concentration, ie, 100 μg/mL. Free DSAP did not cause lytic effects at concentrations up to 50 μg/mL as previously observed.10 The BBE particle did not lyse RBCs even at 100 μg/mL (Figure 2a).


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)

Free non-particulate ASAP causes early cell destruction but not the particulate form. A) Cell destruction measured by hemolytic effect. KGI and BBE are virtually non-lytic while free ASAP is highly lytic. B) Free ASAP induces early cell death in human normal monocytes like in cancer cells, but not the ASAP formulated into KGI particles measured by Trypan Blue staining. C) Free ASAP induces early cell death in U937 tumor cells within minutes at the concentrations indicated. KGI does not induce this rapid cell death. D) Cell membrane destruction measured by the release of the intracellular enzyme thymidine kinase (TK) to the extracellular medium. Free ASAP causes TK release, while KGI does not cause the leakage. E) Free ASAP causes cell necrosis but not KGI particles.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-5-051: Free non-particulate ASAP causes early cell destruction but not the particulate form. A) Cell destruction measured by hemolytic effect. KGI and BBE are virtually non-lytic while free ASAP is highly lytic. B) Free ASAP induces early cell death in human normal monocytes like in cancer cells, but not the ASAP formulated into KGI particles measured by Trypan Blue staining. C) Free ASAP induces early cell death in U937 tumor cells within minutes at the concentrations indicated. KGI does not induce this rapid cell death. D) Cell membrane destruction measured by the release of the intracellular enzyme thymidine kinase (TK) to the extracellular medium. Free ASAP causes TK release, while KGI does not cause the leakage. E) Free ASAP causes cell necrosis but not KGI particles.
Mentions: The cell membrane lytic effect of the ASAP and DSAP or their particulate forms the KGI and BBE was measured on RBCs. Free ASAP lysed RBCs at a concentration of 5 μg/mL (Figure 2a) whereas the KGI particles induced RBC lysis at a 20-fold higher concentration, ie, 100 μg/mL. Free DSAP did not cause lytic effects at concentrations up to 50 μg/mL as previously observed.10 The BBE particle did not lyse RBCs even at 100 μg/mL (Figure 2a).

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