Anti-cancer effects of 20(S)-protopanoxadiol on human acute lymphoblastic leukemia cell lines Reh and RS4;11

Sun, Lihua; Wang, Qiong; Liu, Xinmin; Brons, Nicolaas H. C.; Wang, Ning; Steinmetz, André; Lv, Yali; Zheng, Huyong

doi:10.1007/s12032-010-9508-1

Cited by 18 publications

(11 citation statements)

References 41 publications

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“…Malignant growth was characterized by uncontrolled cell cycle and loss of cell cycle check points. There are two major check points in cell cycle, the G1/S transition and the G2/M transition (Sun et al 2011).…”

Section: Discussionmentioning

confidence: 99%

The anti-tumor activity of Mikania micrantha aqueous extract in vitro and in vivo

Dou¹,

Sun²,

et al. 2013

Cytotechnology

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Aqueous extract obtained from Mikania micrantha (MMAE) is commonly used as traditional medicine in some countries. We hypothesized that MMAE may inhibit tumor cell growth, both in an in vitro and in vivo setting. In in vitro experiments, two kinds of human cancer cell lines, K562 and Hela were used to test the anti-tumor activity. Inhibitory concentrations (IC50) were obtained from the inhibition curves fitted by regression analysis, inhibitory rates (%) were calculated by MTT assay, morphological changes were observed by transmission electron microscope (TEM), cell cycles were analyzed by flow cytometry (FCM), and DNA ladders were determined by agarose gel electrophoresis. The in vivo anti-tumor activity was evaluated by calculating the tumor inhibitory rates, thymus index and spleen index of S180-bearing mice. Paraffin-embedded sections were used to test the pathologic changes. The result displayed that the growth of K562 and Hela were enhanced when treated with MMAE at 20 μg/mL after 48 h. Other concentrations of MMAE (50, 100, 200, 400 μg/mL) inhibited the proliferation of both kinds of cells. The IC50 values of K562 and Hela at 48 h were 167.16 and 196.27 μg/mL and at 72 h 98.07 and 131.56 μg/mL, respectively. The effects showed time-dose dependence. MMAE led to damages of organelles and induced apoptosis. These results were confirmed by ladder DNA fragmentation profile. MMAE also increased the percentage of cells in G2/M phase and decreased the percentage of cells undergoing G0/G1 and S phase in in vivo tests using S180 cells. MMAE showed antitummor activity in vivo, with its tumor inhibitory rate ranging from 12.1 to 46.9 %. MMAE also induced necrosis, as shown by pathological examination of Hematoxilin-Eosin stained tumor sections. Meanwhile, compared with the control group, the changes of thymus index and spleen index in MMAE treated group were not obvious. This study suggests that MMAE may be an effective agent for cancer therapy with low toxicity.

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Section: Discussionmentioning

confidence: 99%

The anti-tumor activity of Mikania micrantha aqueous extract in vitro and in vivo

Dou¹,

Sun²,

et al. 2013

Cytotechnology

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“…20 (S)-protopanoxadiol was reported to stimulate differentiation and inhibit growth and cell cycle progression of ALL cell line Reh and RS4;11 [30]. In vivo studies are warranted.…”

Section: Promising New Treatmentsmentioning

confidence: 99%

Acute Lymphoblastic Leukemia of Adulthood: Progress or Not?

Wiernik

2011

Curr. Treat. Options in Oncol.

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Much new information about ALL in adults has recently been learned from major clinical and laboratory studies. However, much of the recently reported improved management of this leukemia pertains only to younger patients. Elderly patients do not fair very well with modern therapy, including intensified treatment approaches. The question arises whether current treatment may be unnecessarily intensive, not only for elderly patients but for most patients. There are no prospective, randomized studies that clearly demonstrate that anthracyclines, cyclophosphamide or cytarabine are required for optimal results in this leukemia. Eliminating drugs of marginal value but with the potential for considerable toxicity may allow us to intensify treatment with drugs that are most effective at a cost of even less toxicity than usually expected.

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“…In order to overcome the poor physicochemical and biopharmaceutical properties of ginsenosides, previous studies have hydrolyzed ginsenosides to afford their aglycones, PPT and PPD. These two aglycones have been shown to improve oral bioavailability and more potent activities relative to their original saponins [3][4][5][6]. For example, PPD has shown enormous potential as a new anti-P450 inhibitory excipient(s)-based self-microemulsion to encapsulate protopanaxatriol and protopanaxadiol so as to enhance the in vivo bioavailability by inhibiting intestinal metabolism.…”

Section: Introductionmentioning

confidence: 99%

Cytochromes P450 Inhibitory Excipient-Based Self-Microemulsions for the Improved Bioavailability of Protopanaxatriol and Protopanaxadiol: Preparation and Evaluation

et al. 2016

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Protopanaxatriol and protopanaxadiol exhibit limited oral bioavailability due to the poor solubility and intestinal cytochromes P450-mediated metabolism. This study set out to develop a novel cytochromes P450 inhibitory excipient(s)-based self-microemulsion to encapsulate protopanaxatriol and protopanaxadiol so as to enhance the bioavailability by inhibiting intestinal metabolism. After screening the inhibitory effect of pharmaceutical excipients on the cytochromes P450-mediated metabolism, two self-microemulsions, SME-1 and SME-2, with similar physicochemical properties were prepared by using either active inhibitory excipients or corresponding inactive excipients. The results showed that no significant difference existed in the profiles of release, cellular uptake, and permeability in Caco-2 cells, and lymphatic transport between self-microemulsion-1 and self-microemulsion-2. The pharmacokinetic experiments indicated that self-microemulsion-1 conferred to significantly higher absolute bioavailability of protopanaxatriol (19.55 %) and protopanaxadiol (100.07 %) than those of the free drug (2.21 % and 23.70 %, respectively) or of self-microemulsion-2 (4.95 % and 45.35 %, respectively). The present work demonstrated that the presence of cytochromes P450 inhibitory excipients in self-microemulsion-1 tended to inhibit intestinal cytochromes P450-mediated metabolism and subsequently improved the oral bioavailability of protopanaxatriol and protopanaxadiol.

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Anti-cancer effects of 20(S)-protopanoxadiol on human acute lymphoblastic leukemia cell lines Reh and RS4;11

Cited by 18 publications

References 41 publications

The anti-tumor activity of Mikania micrantha aqueous extract in vitro and in vivo

The anti-tumor activity of Mikania micrantha aqueous extract in vitro and in vivo

Acute Lymphoblastic Leukemia of Adulthood: Progress or Not?

Cytochromes P450 Inhibitory Excipient-Based Self-Microemulsions for the Improved Bioavailability of Protopanaxatriol and Protopanaxadiol: Preparation and Evaluation

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