Bullatacin, a potent antitumor Annonaceous acetogenin, induces apoptosis through a reduction of intracellular cAMP and cGMP levels in human hepatoma 2.2.15 cells

Chiu, Hui Fen; Chih, T.-T.; Hsian, Yun Mei; Tseng, Chih Hua; Wu, Ming; Wu, Yang Chang

doi:10.1016/s0006-2952(02)01554-x

Cited by 47 publications

(25 citation statements)

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“…Weak staining of some of the cells with annexin V was probably because of a limited phosphatidylserine exposure during the early stage of apoptosis. 47 The heavily stained annexin V and propidium iodide cells indicated the later phase of the apoptotic process, whereby the cells lost their plasma membrane integrity, and more binding sites of phosphatidylserine were detected. 45 In conclusion, the anticancer property of the P minima plant has been partially validated by identifying the apoptotic cell death mechanism elicited by its chloroform extract against T-47D cells.…”

Section: Discussionmentioning

confidence: 99%

Apoptotic Effects of Physalis minima L. Chloroform Extract in Human Breast Carcinoma T-47D Cells Mediated by c-myc-, p53-, and Caspase-3-Dependent Pathways

et al. 2010

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The chloroform extract of Physalis minima produced a significant growth inhibition against human T-47D breast carcinoma cells as compared with other extracts with an EC 50 value of 3.8 mg/mL. An analysis of cell death mechanisms indicated that the extract elicited an apoptotic cell death. mRNA expression analysis revealed the coregulation of apoptotic genes, that is, c-myc, p53, and caspase-3. The c-myc was significantly induced by the chloroform extract at the earlier phase of treatment, followed by p53 and caspase-3. Biochemical assay and ultrastructural observation displayed typical apoptotic features in the treated cells, including DNA fragmentation, blebbing and convolution of cell membrane, clumping and margination of chromatin, and production of membrane-bound apoptotic bodies. The presence of different stages of apoptotic cell death and phosphatidylserine externalization were further reconfirmed by annexin V and propidium iodide staining. Thus, the results from this study strongly suggest that the chloroform extract of P minima induced apoptotic cell death via p53-, caspase-3-, and c-myc-dependent pathways.

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Section: Discussionmentioning

confidence: 99%

Apoptotic Effects of Physalis minima L. Chloroform Extract in Human Breast Carcinoma T-47D Cells Mediated by c-myc-, p53-, and Caspase-3-Dependent Pathways

et al. 2010

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“…Induction of apoptosis by GC-51 in HL-60 cells was PKA dependent Bullatacin, a bioactive component isolated from Annonaceous, induces cell apoptosis by reducing the intracellular cAMP level [14] . Thus, we tested the role of cAMP in GC-51-induced HL-60 cell apoptosis.…”

Section: Downregulation Of Bcl-2 Mrna Expression By Gc-51mentioning

confidence: 99%

Induction of leukemia cell apoptosis by cheliensisin A involves downregulation of Bcl-2 expression

Zhong

Hao

et al. 2005

Acta Pharmacol Sin

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Aim: To investigate the apoptosis-inducing effect of cheliensisin A (GC-51), a novel styryl-lactone isolated from Goniothalamus cheliensis, on human promyelocytic leukemia HL-60 cells and the mechanism of action involved. Methods: Apoptotic cell death was determined by morphological examination and DNA agarose gel electrophoresis. The activity of caspase-3 was assessed using Western blotting and the expression of Bcl-2 and Bax genes was analyzed using the reverse transcription-polymerase chain reaction (RT-PCR) method. Results: GC-51 significantly inhibited the proliferation of HL-60 cells with an IC 50 of 2.4±0. 2 ìmol/L and effectively induced apoptosis in HL-60 cells. Exposure of HL-60 cells to 10 ìmol/L GC-51 for 8 h resulted in approximately 53% of the cells undergoing apoptosis. Caspase-3 was activated in GC-51-treated cells, which was manifested by the appearance of the 17 kDa active form of caspase-3 and the cleavage of poly(ADP-ribose) polymerase (PARP). Meanwhile, GC-51 markedly reduced the expression of the anti-apoptotic gene Bcl-2 and increased the expression of the pro-apoptotic gene Bax. The apoptosis-inducing effect of GC-51 was cAMPdependent protein kinase (PKA) dependent because PKA, but not the protein kinase C, specific inhibitor H-89, blocked the induction of apoptosis by GC-51 in HL-60 cells. Conclusion: The results demonstrate that GC-51 effectively induces apoptosis in HL-60 cells and that this effect is PKA-dependent and involves the downregulation of Bcl-2 expression and the activation of caspase-3.

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“…8 The three bis-tetrahydrofuran compounds from Annona squamosa seeds showed 50% inhibitory concentration (IC 50 ) values that were one to two orders of magnitude less than fluorouracil against SMMC 7721 (human hepatocellular carcinoma), HeLa (human cervix carcinoma), MKN-45 (human gastric cancer), and HepG2 (human hepatocellular carcinoma) cell lines. 9 It was demonstrated that ACGs exerted antitumor effects via inhibition of mitochondrial complex I (NADH:ubiquinone oxidoreductase) of the electron transport chain, 10,11 which might favor reversing multiple drug resistance in many tumor cell lines because multiple drug resistance is an energy-consuming process. 12 In vivo tests in mice showed the antitumor effects and even some possible adverse effects of ACGs.…”

Section: Introductionmentioning

confidence: 99%

Annonaceous acetogenins nanosuspensions stabilized by PCL–PEG block polymer: significantly improved antitumor efficacy

Hong

Li²,

et al. 2016

IJN

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Annonaceous acetogenins (ACGs) have shown superior antitumor activity against a variety of cancer cell lines, but their clinical application has been limited by their poor solubility. In this study, ACGs-nanosuspensions (NSps) were successfully prepared by a precipitation ultrasonic method using monomethoxypoly (ethylene glycol)2000–poly (ε-caprolactone)2000 (mPEG2000–PCL2000) as a stabilizer. The resultant ACGs-NSps had a mean particle size of 123.2 nm, a zeta potential of −20.17 mV, and a high drug payload of 73.68%. ACGs-NSps were quite stable in various physiological solutions, and they exhibited sustained drug release. Compared to free drug, ACGs-NSps exhibited stronger cytotoxicity against 4T1, MCF-7, and HeLa cells. An in vivo real-time biodistribution investigation after labeling with 1,1′-dioctadecyltetramethyl indotricarbocyanine iodide, a noninvasive near-infrared fluorescence probe, demonstrated that ACGs-NSps could effectively accumulate in tumor. An in vivo antitumor activity study in 4T1 tumor-bearing mice revealed that ACGs-NSps achieved much better therapeutic efficacy than the traditional dosage form (oil solution) even at 1/10 of the dose (74.83% vs 45.53%, P <0.05), demonstrating that NSp was a good dosage form for ACGs to treat cancer.

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Bullatacin, a potent antitumor Annonaceous acetogenin, induces apoptosis through a reduction of intracellular cAMP and cGMP levels in human hepatoma 2.2.15 cells

Cited by 47 publications

References 45 publications

Apoptotic Effects of Physalis minima L. Chloroform Extract in Human Breast Carcinoma T-47D Cells Mediated by c-myc-, p53-, and Caspase-3-Dependent Pathways

Apoptotic Effects of Physalis minima L. Chloroform Extract in Human Breast Carcinoma T-47D Cells Mediated by c-myc-, p53-, and Caspase-3-Dependent Pathways

Induction of leukemia cell apoptosis by cheliensisin A involves downregulation of Bcl-2 expression

Annonaceous acetogenins nanosuspensions stabilized by PCL–PEG block polymer: significantly improved antitumor efficacy

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Bullatacin, a potent antitumor Annonaceous acetogenin, induces apoptosis through a reduction of intracellular cAMP and cGMP levels in human hepatoma 2.2.15 cells

Cited by 47 publications

References 45 publications

Apoptotic Effects of Physalis minima L. Chloroform Extract in Human Breast Carcinoma T-47D Cells Mediated by c-myc-, p53-, and Caspase-3-Dependent Pathways

Apoptotic Effects of Physalis minima L. Chloroform Extract in Human Breast Carcinoma T-47D Cells Mediated by c-myc-, p53-, and Caspase-3-Dependent Pathways

Induction of leukemia cell apoptosis by cheliensisin A involves downregulation of Bcl-2 expression

Annonaceous acetogenins nanosuspensions stabilized by PCL&ndash;PEG block polymer: significantly improved antitumor efficacy

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Annonaceous acetogenins nanosuspensions stabilized by PCL–PEG block polymer: significantly improved antitumor efficacy