Cytotoxic and proapoptotic activity of ent-16β-17α-dihydroxykaurane on human mammary carcinoma cell line MCF-7

Morales, Alvaro; Pérez, Pedro J.; Mendoza, Rafael Muci; Compagnone, Reinaldo S.; Suárez, Alírica I.; Arvelo, Francisco; Ramı́rez, José Luis; Galindo-Castro, Iván

doi:10.1016/j.canlet.2004.07.009

Cited by 35 publications

(30 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, eriocalyxin B induces apoptosis against four pancreatic adenocarcinoma cell lines (PANC-1, SW1990, CAPAN-1, and CAPAN-2), 22) 13-hydroxy-15-oxo-zoapatlin induces apoptosis in human leukemia (U937 and Molt4), 23) weisiensin B induces apoptosis in human hepatoma (BEL-7402), 24) ponicidin induces apoptosis in lung cancer (A549 and GLC-82), 25) and ent-16β-17α-dihydroxykaurane induces apoptosis in breast cancer (MCF-7). 8) In this study, we found that CrT1 treatment caused apoptosis in SK-HEP1 cells (Figs. 2A, B).…”

Section: Discussionmentioning

confidence: 60%

“…Previous studies have indicated that ent-kaurane diterpenoids have anticancer activity. 7,8,21) In this study, we found that a major ent-kaurane diterpenoid, CrT1, isolated from Vietnamese plant Croton tonkinensis, inhibited proliferation and enhanced apoptosis in human hepatocellular carcinoma SK-HEP1 cells. Our results showed that CrT1 induced cell death in SK-HEP1 cancer cells, as determined by the CCK-8 assay (Figs.…”

Section: Discussionmentioning

confidence: 73%

“…4,7) Among them, the ent-kaurane diterpenoids have cytotoxic and proapoptotic activities, 8) inhibit lipopolysaccharide-induced nuclear factor kappa B activation, 9) reduce inflammation, 10) inhibit silent information regulator two ortholog 1 (SIRT1), 11) and stimulate osteoblast differentiation. 12) AMP-activated protein kinase (AMPK) is a cellular energy status sensor found in all eukaryotes, which is activated under conditions of low intracellular ATP following stressors such as nutrient deprivation and hypoxia.…”

mentioning

confidence: 99%

See 2 more Smart Citations

An ent-Kaurane Diterpenoid from Croton tonkinensis Induces Apoptosis by Regulating AMP-Activated Protein Kinase in SK-HEP1 Human Hepatocellular Carcinoma Cells

Sul

Lee

Young

et al. 2013

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with high mortality worldwide. Traditional chemotherapy for HCC is not widely accepted by clinical practitioners because of its toxic side effects. Thus, there is a need to identify chemotherapeutic drugs against HCC. AMP-activated protein kinase (AMPK) is a biologic sensor for cellular energy status that acts a tumor suppressor and a potential cancer therapeutic target. The traditional Vietnamese medicinal plant Croton tonkinensis shows cytotoxicity in various cancer cells; however, its anticancer mechanism remains unclear. In this study, we determined whether the ent-kaurane diterpenoid ent-18-acetoxy-7β-hydroxy kaur-15-oxo-16-ene (CrT1) isolated from this plant plays a role as a chemotherapeutic drug targeting AMPK. CrT1 blocked proliferation in dose-and time-dependent manners in human hepatocellular carcinoma SK-HEP1 cells. CrT1 induced sub-G 1 arrest and caspase-dependent apoptosis. CrT1 activated caspase-3, -7, -8, -9, and poly(ADP-ribose) polymerase, and its effect was inhibited by z-VAD-fmk suppressing caspase-3 cleavage. CrT1 induced increases in p53 and Bax levels but decreased Bcl 2 levels. In addition, CrT1 resulted in increased translocation of cytochrome c into the cytoplasm. We showed that CrT1-activated AMPK activation was followed by modulating the mammalian target of rapamycin/p70S6K pathway and was inactivated by treating cells with compound C. Treatment with CrT1 and aminoimidazole carboxamide ribonucleotide (AICAR) synergistically activated AMPK. CrT1-induced AMPK activation regulated cell viability and apoptosis. These results suggest that CrT1 is a novel AMPK activator and that AMPK activation in SK-HEP1 cells is responsible for CrT1-induced anticancer activity including apoptosis.Key words hepatocellular carcinoma; AMP-activated protein kinase; ent-kaurane diterpenoid Hepatocellular carcinoma (HCC) is the most common type of liver cancer with high mortality and causes 662000 deaths worldwide each year. To date, HCC has a life-threatening and unsatisfactory prognosis. Once the diagnosis is confirmed, most patients are already at the advanced stage and have lost the opportunity for surgical intervention. Further characterization of underlying molecular mechanisms in HCC would bring new insights into HCC research and clinical treatment.

show abstract

Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 73%

mentioning

confidence: 99%

See 1 more Smart Citation

An ent-Kaurane Diterpenoid from Croton tonkinensis Induces Apoptosis by Regulating AMP-Activated Protein Kinase in SK-HEP1 Human Hepatocellular Carcinoma Cells

Sul

Lee

Young

et al. 2013

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that extracts from several Croton species such C. zambesicus, C. argyratus, and C. pierrei induce apoptosis, and these extracts are used in the management of tumors (Sandoval et al, 2002;Block et al, 2005;Morales et al, 2005). Several studies have proven the efficacy of beta-sitosterol and its glycosides in inhibiting the growth and improving the symptoms of BPH and prostate cancer (Wilt et al, 2000;Awad et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Mitochondria-dependent apoptogenic activity of the aqueous root extract of Croton membranaceus against human BPH-1 cells

Afriyie¹,

Asare²,

Bugyei³

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT.Croton membranaceus aqueous root extract (CMARE) is among the widely used phytotherapeutics in Ghana for the management of benign prostatic hyperplasia (BPH) and prostate cancer. However, the mechanism of action of CMARE remains to be elucidated. This study aimed to establish whether apoptosis is involved in the antiproliferative effect of CMARE on human BPH-1 cells. We determined the effect of treatment with 0, 1, 3, and 5 mg/mL CMARE for 24, 48, and 72 h on the viability and morphology of BPH-1 cells using the MMT assay and phase-contrast microscopy, respectively. We examined the apoptosisinducing effects of CMARE after 48 h at the cellular level using Hoescht 33258 and JC-1 dye staining and flow cytometry analysis. We performed reverse transcription polymerase chain reaction and Western blotting to confirm the apoptotic effects of CMARE at the molecular level. CMARE induced a significant dose-dependent inhibition in the proliferation of BPH-1 cells (P < 0.05) and an alteration in their morphology and a reduction their density. Furthermore, CMARE induced dose-dependent staining of the nuclear chromatin, significant DNA fragmentation with G 0 /G 1 sub-diploid cells (P < 0.01), and loss of the mitochondrial membrane potential in the treated cells compared to the controls after 48 h (P < 0.01). Additionally, while CMARE induced a significant upregulation of the mRNA and protein levels of Bax, those of Bcl 2 did not change significantly. Therefore, induction of mitochondria-dependent apoptosis of BPH-1 cells may be a possible mechanism of action of CMARE.

show abstract

“…Kaurene diterpenes exhibit toxicity against tumor cells through various methods. The ent-kaurene diterpenoid ent-16β-17α-dihydroxykaurane triggered apoptosis of MCF-7 cells by a decrease in telomerase mRNA (24). Oridonin, ponicidin, xindongnin A and xindoninin have been demonstrated to be potent inhibitors of NF-κB transcription activity (25).…”

Section: Discussionmentioning

confidence: 99%

Glaucocalyxin A inhibits the growth of liver cancer Focus and SMMC-7721 cells

Tang

Jin

et al. 2015

Oncology Letters

View full text Add to dashboard Cite

Abstract. Liver cancer is one of the most common types of cancer, and hepatoma demonstrates a poor long-term prognosis. The present study reports that glaucocalyxin A (GLA), a natural product isolated from Rabdosia umbrosa, inhibits the growth of the liver cancer Focus and SMMC-7721 cell lines in a dose-and time-dependent manner. The present study revealed that GLA arrested the liver cancer cells at the G2/M stage of the cell cycle and led to decreased expression of caspase 3 and the cleavage of poly(adenosine diphosphate-ribose) polymerase.Overall, the present study demonstrated that GLA inhibits the growth of liver cancer cells by G2/M stage cell-cycle arrest and cell apoptosis.

show abstract

Cytotoxic and proapoptotic activity of ent-16β-17α-dihydroxykaurane on human mammary carcinoma cell line MCF-7

Cited by 35 publications

References 25 publications

An <i>ent</i>-Kaurane Diterpenoid from <i>Croton tonkinensis</i> Induces Apoptosis by Regulating AMP-Activated Protein Kinase in SK-HEP1 Human Hepatocellular Carcinoma Cells

An <i>ent</i>-Kaurane Diterpenoid from <i>Croton tonkinensis</i> Induces Apoptosis by Regulating AMP-Activated Protein Kinase in SK-HEP1 Human Hepatocellular Carcinoma Cells

Mitochondria-dependent apoptogenic activity of the aqueous root extract of Croton membranaceus against human BPH-1 cells

Glaucocalyxin A inhibits the growth of liver cancer Focus and SMMC-7721 cells

Contact Info

Product

Resources

About