Selective inhibition of human leukemia cell growth and induction of cell cycle arrest and apoptosis by pseudolaric acid B

Ma, Guoyi; Li, Chong; Li, Xing-Cong; Khan, Ikhlas A.; Walker, Larry; Khan, Shabana I.

doi:10.1007/s00432-010-0784-0

Cited by 26 publications

(19 citation statements)

References 26 publications

(35 reference statements)

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“…To date, several pharmacological reports have shown that PLAB induces growth inhibition, cell cycle arrest, and apoptosis in a number of cancer cell lines including breast cancer, colon cancer, hepatocellular carcinoma, melanoma cells [9], liver cancer, cervical cancer, gastric cancer, lung cancer, and leukemia [10, 11]. Further studies have shown that PLAB induces apoptosis via activation of c-Jun N-terminal kinase and caspase-3 in HeLa cells [12], through p53 upregulation in gastric carcinoma MGC803 cells [11], through Bcl-2 downregulation and caspase-3 activation in AGS gastric cancer cells [13], through p53 and Bax/Bcl-2 pathways in human melanoma A375-S2 cells [12] and through activation of JNK and inactivation of ERK in breast cancer MCF-7 cells [9].…”

Section: Introductionmentioning

confidence: 99%

Pseudolaric Acid B Induces Caspase-Dependent and Caspase-Independent Apoptosis in U87 Glioblastoma Cells

Khan

Zheng

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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Pseudolaric acid B (PLAB) is one of the major bioactive components of Pseudolarix kaempferi. It has been reported to exhibit inhibitory effect on cell proliferation in several types of cancer cells. However, there is no report elucidating its effect on glioma cells and organ toxicity in vivo. In the present study, we found that PLAB inhibited growth of U87 glioblastoma cells in a dose-dependent manner with IC50 ~10 μM. Flow cytometry analysis showed that apoptotic cell death mediated by PLAB was accompanied with cell cycle arrest at G2/M phase. Using Western blot, we found that PLAB induced G2/M phase arrest by inhibiting tubulin polymerization in U87 cells. Apoptotic cell death was only partially inhibited by pancaspase inhibitor, z-VAD-fmk, which suggested that PLAB-induced apoptosis in U87 cells is partially caspase-independent. Further mechanistic study demonstrated that PLAB induced caspase-dependent apoptosis via upregulation of p53, increased level of proapoptotic protein Bax, decreased level of antiapoptotic protein Bcl-2, release of cytochrome c from mitochondria, activation of caspase-3 and proteolytic cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-independent apoptosis through apoptosis inducing factor (AIF). Furthermore, in vivo toxicity study demonstrated that PLAB did not induce significant structural and biochemical changes in mouse liver and kidneys at a dose of 25 mg/kg. Therefore, PLAB may become a potential lead compound for future development of antiglioma therapy.

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Section: Introductionmentioning

confidence: 99%

Pseudolaric Acid B Induces Caspase-Dependent and Caspase-Independent Apoptosis in U87 Glioblastoma Cells

Khan

Zheng

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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“…The Jurkat cell line, a human leukaemia cell line, was included in the analysis as leukaemias are a prevalent form of childhood cancers (Ma et al, 2010). Also, coumarins (the type of compound that the PST was found to be rich in, not shown) have been suggested as potential lead candidates for the treatment of haematological malignancies (Riviero et al, 2008).…”

Section: Anti-proliferative Activitymentioning

confidence: 99%

Activity-guided isolation and identification of the major antioxidant and anticancer compounds from a commercial Pelargonium sidoides tincture

et al. 2015

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Extracts prepared from the roots of Pelargonium sidoides (DC) are commercially available for the treatment of respiratory related conditions. Recently, a commercial radix mother tincture of this plant was shown to have both antioxidant and anticancer effects especially related to the G 0 /G 1 block in the Jurkat E6.1 cell line (unpublished results). Fractions were prepared by semi-preparative HPLC, and their antioxidant and anticancer activities were determined. The more hydrophilic fractions isolated namely F6-F12 were all found to have strong reducing capacities and were able to scavenge peroxyl radicals. In the human lung cell line, NCI-H460, significant cellular antioxidant effects were observed. Anticancer activity was evaluated in the NCI-pre-screen panel (NCI-H460, MCF-7 and SF-268) and the Jurkat E6.1 cell line. Fractions F7, F9 and F12 were found to inhibit the cell growth of these four 1 cell-lines (p < 0.05), especially the Jurkat E6.1 cell line with the sulforhodamine B assay.Mass spectrometry analysis revealed that these active fractions contained several polyphenolic compounds such as gallic acid, trihydroxycoumarin, dihydroxycoumarin sulfates, proanthocyanidins and phenolic glycosides. A phenolic acid glycoside sulfate not previously shown in Pelargonium sidoides extracts was also isolated. In conclusion, the antioxidant and/or anticancer activity of the Pelargonium sidoides tincture may be attributed to the presence of these polyphenolics.

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“…PAB is a diterpene acid isolated from the root and trunk bark of Pseudolarix kaempferi and possesses multiple biological and pharmacological activities, including antifungal, antimicrobial, antifertility and antiangiogenic properties (10)(11)(12)(13)(14)(15). It has been previously confirmed that PAB exhibits an antitumor effect by inducing apoptosis in various types of cancer (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Apoptosis is important in homeostasis maintenance through a balance between cell proliferation and cell death (28).…”

Section: Discussionmentioning

confidence: 99%

“…In murine fibrosarcoma L929 cells, PAB promotes proliferation, inhibits apoptosis and arrests the cell cycle at the G2/M phase by downregulating the Bcl-2 and CDC2 proteins (23,24). In HL-60 human leukemia cells, PAB inhibits proliferation and induces apoptosis by arresting cells at the G2/M phase of the cell cycle and activating of caspase-3 (25). In DU145 hormone-refractory prostate cancer cells, PAB induced apoptosis by activating caspase-3 and -9 and downregulating Bcl-2 (26).…”

Section: Introductionmentioning

confidence: 99%

Role of pseudolaric acid B in A549 lung cancer cell proliferation and apoptosis

Guan

Yang

2013

Molecular Medicine Reports

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Abstract. Recently, traditional Chinese medicine has gained attention for its potential use as a chemotherapeutic agent. Pseudolaric acid B (PAB) is a diterpene acid isolated from Pseudolarix kaempferi and possesses antifungal, antimicrobial, antifertility and antiangiogenic properties. It was also reported that PAB may inhibit proliferation and induce apoptosis in various types of cancer. However, its effects on A549 lung cancer cells remain to be determined. The present study aimed to determine the potential roles of PAB in the proliferation and apoptosis of A549 cells. The results showed that PAB inhibited A549 cell proliferation in a time-and dose-dependent manner. Fluorescence microscopy results showed that cells treated with 20 µmol/l PAB for 24 h exhibited karyorrhexis and apoptotic body formation. In addition, A549 cells were treated with 5, 10, 20, 40 or 80 µmol/l PAB for 24 h and apoptosis was analyzed using Annexin-V/propidium iodide kit. The apoptosis rates were 8. 95, 18.71, 24.66, 35.02 and 43.64%, respectively, in PAB-treated cells and 0.80% in the control group. Furthermore, western blot analysis showed that PAB treatment upregulated the protein levels of Bax, Bad and downregulated Bcl-2 and Bcl-xl expression. In conclusion, PAB may serve as a potent chemotherapeutic agent against human lung cancer.

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Selective inhibition of human leukemia cell growth and induction of cell cycle arrest and apoptosis by pseudolaric acid B

Abstract: This study indicates that PAB has a potential for use against leukemia and its effects might be mediated by inhibiting tubulin polymerization, preventing cell division and activating caspase-3, which leads to apoptosis.

Cited by 26 publications

References 26 publications

Pseudolaric Acid B Induces Caspase-Dependent and Caspase-Independent Apoptosis in U87 Glioblastoma Cells

Pseudolaric Acid B Induces Caspase-Dependent and Caspase-Independent Apoptosis in U87 Glioblastoma Cells

Activity-guided isolation and identification of the major antioxidant and anticancer compounds from a commercial Pelargonium sidoides tincture

Role of pseudolaric acid B in A549 lung cancer cell proliferation and apoptosis

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