Ha-rasVal12Oncogene Increases Susceptibility of NIH/3T3 Cells to Lovastatin

Chang, Meng-Yao; Jan, Ming‐Shiou; Won, Shen‐Jeu; Liu, Hsiao Sheng

doi:10.1006/bbrc.1998.8911

Cited by 32 publications

(11 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, we also demonstrated the caspase-3 activity was stimulated, but not caspase-1 protease by lovastatin treatment. Re- cently, similar results were observed in NIH/3T3 cells (Chang et al 1998). Caspase-3 is one of the strongest candidates for the mammalian apoptotic protease cleavage of PARP (Kumar & Harvey 1995).…”

Section: Discussionsupporting

confidence: 74%

Induction of Apoptosis by Lovastatin through Activation of Caspase‐3 and DNase II in Leukaemia HL‐60 Cells

Wang¹,

Lin‐Shiau²,

Lin³

2000

Pharmacology & Toxicology

View full text Add to dashboard Cite

Lovastatin, an HMG-CoA reductase inhibitor, was found to suppress growth and induce apoptosis in culture human promyelocytic leukaemic cell, HL-60. However, the mechanisms of lovastatin-induced apoptosis are still unclear. In this study, we attempted to elucidate the signal transduction pathway for lovastatin-induced apoptosis in HL-60 cells in a dose-and time-dependent manner. The features of this apoptosis were attenuated by the presence of mevalonate, a metabolic intermediate of cholesterol synthesis. Treatment of lovastatin caused a rapid release of mitochondrial cytochrome c into cytosol and subsequent induction of caspase-3, but not caspase-1 activity. Lovastatin also stimulated proteolytic cleavage of poly-(ADP-ribose) polymerase (PARP), and followed by the appearance of caspase activity and DNA fragmentation. Pretreatment with caspase-3 inhibitors, Ac-DEVD-CHO and Z-VAD-FMK, inhibited lovastatininduced caspase-3 activity and DNA fragmentation. Furthermore, we demonstrated that DNase II was involved in the DNA fragmentation induced by lovastatin. These results suggested that the mechanism of lovastatin induced HL-60 cells apoptosis through activation of caspase-3 and DNase II activities.

show abstract

Section: Discussionsupporting

confidence: 74%

Induction of Apoptosis by Lovastatin through Activation of Caspase‐3 and DNase II in Leukaemia HL‐60 Cells

Wang¹,

Lin‐Shiau²,

Lin³

2000

Pharmacology & Toxicology

View full text Add to dashboard Cite

show abstract

“…Growing evidence indicates that transformed cells are much more sensitive than normal cells to growth-inhibitory and apoptotic effects of HDACIs (6,47). Other evidence has shown that anticancer agents, including 5-fluorouracil (48), etoposide VP16 (49), cisplatin (50), lovastatin (51), and arsenic (52), selectively induce apoptosis of oncogenic H-Ras -expressed cells. Our studies verified the proapoptotic activity of oncogenic H-Ras that facilitated HDACIs to induce cell death of human urinary bladder cancer J82 cells.…”

Section: Proapoptotic Ability Of Ras To Hdacimentioning

confidence: 99%

Proapoptotic ability of oncogenic H-Ras to facilitate apoptosis induced by histone deacetylase inhibitors in human cancer cells

Choudhary

Wang

2007

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…The modulating effects of butyrate and lovastatin on p21 Waf1 expression were previously reported. 16,25 Rather surprising effects of the combined treatment on the expression of cyclin D1 were observed. The block in G2/M phase was accompanied by the complete 749 disappearance of cyclin D1 (which is required for S phase entry) in cells treated with both combinations.…”

Section: Discussionmentioning

confidence: 99%

Potentiating antitumor effects of a combination therapy with lovastatin and butyrate in the Lewis lung carcinoma model in mice

Giermasz¹,

Makowski²,

Kozłowska³

et al. 2001

Intl Journal of Cancer

View full text Add to dashboard Cite

Lovastatin, the drug used for the treatment of hypercholesterolemia, has previously been reported to exert antitumor activity in experimental murine models. Butyrate and butyric acid derivatives are well known to induce differentiation and apoptosis of tumour cells and also have recently gained acceptance as potential anticancer agents. In this study, we examined the antitumor effects of the combination of lovastatin and butyrate or its prodrug tributyrin in vitro and in vivo against a murine Lewis lung carcinoma (3LL). This combination therapy showed synergistic antitumor activity against 3LL cells in vitro. These effects were at least in part due to apoptosis induction that occurred after 12 hr of incubation with lovastatin and butyrate and was preceded by changes in cell cycle distribution of treated cells and expression of p21, p53 and cyclin D1. Remarkably, a systemic treatment of syngeneic mice inoculated with 3LL cells with both drugs resulted in significant tumour growth retardation.

show abstract

Ha-rasVal12Oncogene Increases Susceptibility of NIH/3T3 Cells to Lovastatin

Cited by 32 publications

References 25 publications

Induction of Apoptosis by Lovastatin through Activation of Caspase‐3 and DNase II in Leukaemia HL‐60 Cells

Induction of Apoptosis by Lovastatin through Activation of Caspase‐3 and DNase II in Leukaemia HL‐60 Cells

Proapoptotic ability of oncogenic H-Ras to facilitate apoptosis induced by histone deacetylase inhibitors in human cancer cells

Potentiating antitumor effects of a combination therapy with lovastatin and butyrate in the Lewis lung carcinoma model in mice

Contact Info

Product

Resources

About