Cytotoxic Activity of Apomine is Due to a Novel Membrane-mediated Cytolytic Mechanism Independent of Apoptosis in the A375 Human Melanoma Cell Line

Overview

Journal Invest New Drugs

Publisher Springer

Specialty Oncology

Date 2006 Oct 7

PMID 17024575

Citations 4

Authors

Alan Pourpak

Robert T Dorr

Ross O Meyers

Marianne B Powell

Steven P Stratton

Affiliations

Soon will be listed here.

Abstract

Apomine, a novel bisphosphonate ester, has demonstrated anticancer activity in a variety of cancer cell lines; however, its mechanism of cytotoxicity is not well understood. Previous work has demonstrated that Apomine induces cell death by activation of caspase-3 in several cancer cell types. However, we have demonstrated that Apomine induces cell death in the A375 human melanoma cell line through a novel membrane-mediated mechanism that is independent of caspase-3 activation. This mechanism of membrane lysis may apply to other bisphosphonates and may be an important mechanism for overcoming resistance to apoptosis. Interestingly, Apomine-mediated cell death in the A375 and UACC 3093 human melanoma cell lines is also independent of N-Ras farnesylation, which was a previously described mechanism of action for Apomine in other cancer cell types. These data suggest that Apomine induces cell death through a novel plasma membrane-mediated cytolytic pathway, independent of caspase-3 activation and N-Ras farnesylation.

Citing Articles

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Outpatient Follow-up and Secondary Prevention for Melanoma Patients.

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Preformulation, formulation, and in vivo efficacy of topically applied apomine.

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References

Decker T, Lohmann-Matthes M . A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods. 1988; 115(1):61-9. DOI: 10.1016/0022-1759(88)90310-9. View

Graaf M, Richel D, van Noorden C, Guchelaar H . Effects of statins and farnesyltransferase inhibitors on the development and progression of cancer. Cancer Treat Rev. 2004; 30(7):609-41. DOI: 10.1016/j.ctrv.2004.06.010. View

Akare S, Martinez J . Bile acid induces hydrophobicity-dependent membrane alterations. Biochim Biophys Acta. 2005; 1735(1):59-67. DOI: 10.1016/j.bbalip.2005.04.006. View

Omholt K, Karsberg S, Platz A, Kanter L, Ringborg U, Hansson J . Screening of N-ras codon 61 mutations in paired primary and metastatic cutaneous melanomas: mutations occur early and persist throughout tumor progression. Clin Cancer Res. 2002; 8(11):3468-74. View

LaRue J, Stratagoules E, Martinez J . Deoxycholic acid-induced apoptosis is switched to necrosis by bcl-2 and calphostin C. Cancer Lett. 2000; 152(1):107-13. DOI: 10.1016/s0304-3835(99)00439-5. View

Bolick S, Landowski T, Boulware D, Oshiro M, Ohkanda J, Hamilton A . The farnesyl transferase inhibitor, FTI-277, inhibits growth and induces apoptosis in drug-resistant myeloma tumor cells. Leukemia. 2003; 17(2):451-7. DOI: 10.1038/sj.leu.2402832. View

Davies H, Bignell G, Cox C, Stephens P, Edkins S, Clegg S . Mutations of the BRAF gene in human cancer. Nature. 2002; 417(6892):949-54. DOI: 10.1038/nature00766. View

Lewis K, Thompson J, Weber J, Robinson W, ODay S, Lutzky J . A phase II open-label trial of apomine (SR-45023A) in patients with refractory melanoma. Invest New Drugs. 2005; 24(1):89-94. DOI: 10.1007/s10637-005-4544-y. View

Lowe L, Senaratne S, Colston K . Induction of apoptosis in breast cancer cells by apomine is mediated by caspase and p38 mitogen activated protein kinase activation. Biochem Biophys Res Commun. 2005; 329(2):772-9. DOI: 10.1016/j.bbrc.2005.02.032. View

10.

Naito K, He Q, Skog S, Tribukait B, Andersson L, Hisazumi H . Effects of adriamycin and hyperthermia on cellular uptake of [3H]thymidine and its significance for the incorporation into DNA. Int J Hyperthermia. 1989; 5(3):329-40. DOI: 10.3109/02656738909140459. View

11.

Mayr C, Sami S, Dorr R . In vitro cytotoxicity and DNA damage production in Chinese hamster ovary cells and topoisomerase II inhibition by 2-[2'-(dimethylamino)ethyl]-1, 2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones with substitutions at the 6 and 7 positions (azonafides). Anticancer Drugs. 1997; 8(3):245-56. DOI: 10.1097/00001813-199703000-00005. View

12.

Rieber M, Bacalao J, Alonso G . Cholera toxin effects on cell growth accompanied by selective alterations in metabolite uptake and modification of cell surface proteins. Cancer Res. 1975; 35(11 Pt 1):3009-13. View

13.

Dignam J, Lebovitz R, Roeder R . Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983; 11(5):1475-89. PMC: 325809. DOI: 10.1093/nar/11.5.1475. View

14.

Alberts D, Hallum 3rd A, Garcia D, Salmon S, Santabarbara P, Niesor E . Phase I pharmacokinetic trial and correlative in vitro phase II tumor kinetic study of Apomine (SR-45023A), a novel oral biphosphonate anticancer drug. Clin Cancer Res. 2001; 7(5):1246-50. View

15.

Thompson F, Emerson J, Olson S, Weinstein R, Leavitt S, Leong S . Cytogenetics of 158 patients with regional or disseminated melanoma. Subset analysis of near-diploid and simple karyotypes. Cancer Genet Cytogenet. 1995; 83(2):93-104. DOI: 10.1016/0165-4608(95)00057-v. View

16.

Flach J, Antoni I, Villemin P, Bentzen C, Niesor E . The mevalonate/isoprenoid pathway inhibitor apomine (SR-45023A) is antiproliferative and induces apoptosis similar to farnesol. Biochem Biophys Res Commun. 2000; 270(1):240-6. DOI: 10.1006/bbrc.2000.2421. View

17.

Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55-63. DOI: 10.1016/0022-1759(83)90303-4. View

18.

Adjei A . Blocking oncogenic Ras signaling for cancer therapy. J Natl Cancer Inst. 2001; 93(14):1062-74. DOI: 10.1093/jnci/93.14.1062. View

19.

Guan X, Zhang H, Yang J, Wang J, Taetle R, Meltzer P . Detection of chromosome 6 abnormalities in melanoma cell lines by chromosome arm painting probes. Cancer Genet Cytogenet. 1998; 107(2):89-92. DOI: 10.1016/s0165-4608(98)00080-6. View

20.

Goydos J, Mann B, Kim H, Gabriel E, Alsina J, Germino F . Detection of B-RAF and N-RAS mutations in human melanoma. J Am Coll Surg. 2005; 200(3):362-70. DOI: 10.1016/j.jamcollsurg.2004.10.032. View