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纳米颗粒 Quillaja saponin 诱导高治疗指数的人白血病细胞系凋亡。

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

机构信息

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

出版信息

Int J Nanomedicine. 2010 Feb 2;5:51-62.

PMID:20161987
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2819906/
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.

摘要

皂素 Quillaja saponaria Molina (QS) 的分数在体外对癌细胞具有细胞毒性活性，但毒性太大，无法在临床上使用。通过将 QS 分数与胆固醇结合形成稳定的纳米粒子，可消除毒性作用。选择了两种 QS 分数进行粒子形成，一种具有酰基链 (ASAP) 用于形成杀伤和生长抑制 (KGI) 粒子，另一种没有酰基链 (DSAP) 用于形成阻断和平衡效应 (BBE) 粒子。KGI 在 10 种细胞系中的 9 种中表现出显著的生长抑制和癌细胞杀伤活性，而 BBE 在一种细胞系中表现出这种活性。单核细胞样淋巴瘤细胞系 U937 被选择用于分析作用模式。低浓度的 KGI（0.5 和 2 微克/毫升）诱导细胞周期不可逆退出、细胞因子产生所测量的分化，最终导致程序性细胞死亡（细胞凋亡）。与正常人单核细胞相比，U937 细胞对 KGI 的敏感性高 30 倍。非毒性的 BBE 以浓度依赖的方式阻断 KGI 的细胞杀伤作用。总之，将 QS 制成纳米粒子有可能成为一类新的抗癌药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb90/2819906/e564a592739b/ijn-5-051f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb90/2819906/84616ac2eeb9/ijn-5-051f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb90/2819906/0a434285afda/ijn-5-051f2a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb90/2819906/e4a908899a00/ijn-5-051f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb90/2819906/a5a88aff81d7/ijn-5-051f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb90/2819906/982f6b6ad8bd/ijn-5-051f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb90/2819906/e564a592739b/ijn-5-051f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb90/2819906/84616ac2eeb9/ijn-5-051f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb90/2819906/0a434285afda/ijn-5-051f2a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb90/2819906/e4a908899a00/ijn-5-051f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb90/2819906/a5a88aff81d7/ijn-5-051f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb90/2819906/982f6b6ad8bd/ijn-5-051f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb90/2819906/e564a592739b/ijn-5-051f6.jpg

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