Cerivastatin demonstrates enhanced antitumor activity against human breast cancer cell lines when used in combination with doxorubicin or cisplatin

Kozar, Katarzyna; Kaminski, Rafal; Legat, Magdalena; Kopec, Maciej; Nowis, Dominika; Skierski, Janusz; Koronkiewicz, Mirosława; Jakóbisiak, Marek; Gołąb, Jakub

doi:10.3892/ijo.24.5.1149

Cited by 41 publications

(45 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The in vitro effects of statins on cancer, cell cycle regulation (13)(14)(15) and apoptosis induction (16)(17)(18)(19) have been shown and cancer cell proliferation suppression has been confirmed (10)(11)(12). Statins also inhibit growth of cancer in vivo and reduce metastasis at clinical doses (20,21).…”

Section: Introductionmentioning

confidence: 99%

Statins induce apoptosis and inhibit proliferation in cholangiocarcinoma cells

Kamigaki

2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. Given the poor prognosis for cholangiocarcinoma, new and effective treatments are urgently needed. HMG-CoA reductase inhibitors (statins) reportedly exert anticancer effects in a variety of diseases, but there have been no reports of these effects in cholangiocarcinoma. In this study, we investigated the utility of statins for cholangiocarcinoma treatment. Proliferation suppression by pitavastatin and atorvastatin was investigated in the human cholangiocarcinoma cell lines HuCCT1 and YSCCC while changes in the cell cycle and intracellular signals were examined by FACS and Western blotting, respectively. Additive proliferation suppression by statins and pre-existing anticancer drugs was also investigated. HuCCT1 and YSCCC cell proliferation was dramatically suppressed by incubation with statins for 72 h or longer. Cell cycle analysis revealed a reduction in the G2M fraction and an increase in the sub-G1 fraction in statin-treated cells, while Western blotting showed increased levels of cleaved caspase-3 and a reduction in p-ERK. Furthermore, statins in combination with gemcitabine, cisplatin and 5-FU showed additive proliferation suppression. In this study, treatment of human cholangiocarcinoma cells with statins induced apoptosis via suppression of the classical MAPK pathway. Together, these results suggest that statins may be a new cholangiocarcinoma treatment option that could potentially enhance the anticancer effect of pre-existing anticancer drugs.

show abstract

Section: Introductionmentioning

confidence: 99%

Statins induce apoptosis and inhibit proliferation in cholangiocarcinoma cells

Kamigaki

2011

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…In vivo studies have revealed that statins can inhibit tumor cell growth, invasion and metasta sis [14][15][16]. In addition, statins sensitize cancer cells to che motherapy drugs [17][18][19]. Lovastatin treatment enhances the antitumor activity of doxorubicin, a common chemo therapeutic agent for a wide range of cancer [20].…”

Section: Introductionmentioning

confidence: 99%

Statins induce apoptosis in ovarian cancer cells through activation of JNK and enhancement of Bim expression

Liu

Liang

Kumar

et al. 2008

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

Purpose Ovarian cancer is the leading cause of death among all gynecological malignancies in Western coun tries. Although therapy for ovarian cancer has been greatly improved in the past 20 years, the overall survival for patients with advanced ovarian cancer has not changed sig niWcantly. The poor survival rates in patients with advanced ovarian cancer are due both to late diagnosis and to lack of eVective drugs for the majority of patients who have a relapse and develop resistance to current chemotherapy agents used for ovarian cancer. Thus, developing and dis covering eVective novel drugs with diVerent molecular structures from conventional chemotherapy agents have become an urgent clinical need.

show abstract

“…[24][25][26][27][28][29][30]45 In fact, the effects of statins on tumor growth under conventional anticancer chemotherapy are not homogenous and depend on the malignant cell lineage, the time of statin-treatment commencement, the statin type and dose, and the antineoplastic agent, among other factors.…”

Section: 35-40mentioning

confidence: 99%

“…In this respect, statins, the most important cholesterol-lowering class of drugs, have been reported as inducers of apoptosis and antitumor activity of antineoplastic drugs, such as carmustine, cisplatin, 5-fluorouracil, doxorubicin, and PTX, and investigated as adjuvants in cancer treatment and prevention. [24][25][26][27][28][29][30][31] Statins lower LDL cholesterol by inhibiting 3-hydroxy-3 methylglutaryl (HMG)-CoA reductase, the rate-limiting step enzyme of cholesterol synthesis. 32,33 Depletion of intracellular cholesterol by statins leads to increased expression of the LDL receptors that play a key role in the drug-targeting properties of native LDL and the LDE-carrier system.…”

Section: Introductionmentioning

confidence: 99%

Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid nanoemulsions in melanoma-bearing mice

Kretzer¹,

Maria²,

Guido³

et al. 2016

IJN

View full text Add to dashboard Cite

Purpose Lipid nanoemulsions (LDEs) that bind to low-density lipoprotein (LDL) receptors used as carriers of paclitaxel (PTX) can decrease toxicity and increase PTX antitumoral action. The administration of simvastatin (Simva), which lowers LDL-cholesterol, was tested as an adjuvant to commercial PTX and to PTX associated with LDE (LDE-PTX). Materials and methods B16F10 melanoma-bearing mice were treated with saline solution or LDE (controls), Simva, PTX, PTX and Simva, LDE-PTX, and LDE-PTX and Simva: PTX dose 17.5 μmol/kg (three intraperitoneal injections, 3 alternate days): Simva 50 mg/kg/day by gavage, 9 consecutive days. Results Compared with saline controls, 95% tumor-growth inhibition was achieved by LDE-PTX and Simva, 61% by LDE-PTX, 44% by PTX and Simva, and 43% by PTX. Simva alone had no effect. Metastasis developed in only 37% of the LDE-PTX and Simva, 60% in LDE-PTX, and 90% in PTX and Simva groups. Survival rates were higher in LDE-PTX and Simva and in LDE-PTX groups. The LDE-PTX and Simva group presented tumors with reduced cellular density and increased collagen fibers I and III. Tumors from all groups showed reduction in immunohistochemical expression of ICAM, MCP-1, and MMP-9; LDE-PTX and Simva presented the lowest MMP-9 expression. Expression of p21 was increased in the Simva, LDE-PTX, and LDE-PTX and Simva groups. In the Simva and LDE-PTX and Simva groups, expression of cyclin D1, a proliferation and survival promoter of tumor cells, was decreased. Therapy with LDE-PTX and Simva showed negligible toxicity compared with PTX and Simva, which resulted in weight loss and myelosuppression. Conclusion Simva increased the antitumor activity of PTX carried in LDE but not of PTX commercial presentation, possibly because statins increase the expression of LDL receptors that internalize LDE-PTX.

show abstract

Cerivastatin demonstrates enhanced antitumor activity against human breast cancer cell lines when used in combination with doxorubicin or cisplatin

Cited by 41 publications

References 0 publications

Statins induce apoptosis and inhibit proliferation in cholangiocarcinoma cells

Statins induce apoptosis and inhibit proliferation in cholangiocarcinoma cells

Statins induce apoptosis in ovarian cancer cells through activation of JNK and enhancement of Bim expression

Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid nanoemulsions in melanoma-bearing mice

Contact Info

Product

Resources

About