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Nanoparticulate Quillaja saponin induces apoptosis in human leukemia cell lines with a high therapeutic index
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology. (Cancer pharmacology and informatics)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology. (Cancer pharmacology and informatics)
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2010 (English)In: International Journal of Nanomedicine, ISSN 1176-9114, E-ISSN 1178-2013, Vol. 5, no 1, 51-62 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2010. Vol. 5, no 1, 51-62 p.
Keyword [en]
Anticancer drug, Apoptosis, Nanoparticle, Quillaja saponin
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-125017ISI: 000283715300005PubMedID: 20161987OAI: oai:DiVA.org:uu-125017DiVA: diva2:318291
Available from: 2010-05-07 Created: 2010-05-07 Last updated: 2017-12-12Bibliographically approved

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Larsson, RolfNygren, Peter

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