Lucanthone

Lucanthone is an endonuclease inhibitor of Apurinic endonuclease-1 (APE-1).

Signaling Pathways >> Autophagy >> Autophagy

Research Areas >> Cancer

APE-1[1]

Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. To investigate the anticancer activity of Lucanthone, cell viability is measured by MTT assay. Lucanthone reduces cell viability to a similar extent in a panel of seven breast cancer cell lines. In addition, a direct comparison reveals that Lucanthone is significantly more potent than Chloroquine (CQ) at reducing breast cancer cell viability with a mean IC50 of 7.2 μM versus 66 μM for CQ. Measurement of cell viability in two representative cell lines (MDA-MB-231 and BT-20) by ATPlite assay and trypan blue exclusion reveals comparable results[2].

Cell viability is assessed by MTT assay. Cells are seeded into 96-well microculture plates at 10,000 cells per well and allowed to attach for 24 h. Cells are then treated with Lucanthone (0, 0.5, 1, 5, 10, 20 and 40 μM), Chloroquine, Vorinostat, or combinations for 72 h. Following drug treatment, MTT is added and cell viability is quantified using a BioTek microplate reader. Effects on cell viability are also determined by measuring ATP levels using the ATPlite assay system and by trypan blue exclusion. Pro-apoptotic effects following in vitro drug exposure are quantified by propidium iodide (PI) staining and fluorescence-activated cell sorting (FACS) analysis of sub-G0/G1 DNA content[2].

[1]. Chowdhury SM, et al. Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme. Nanomedicine. 2015 Jan;11(1):109-18.

[2]. Carew JS, et al. Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.

Rapamycin (Sirolimus) | MG-132 | Cycloheximide | 3-Methyladenine | LY294002 | TAK-242 | (+)-JQ1 | SB203580 | Pyrazolanthrone (SP600125) | U0126-EtOH | Actinomycin D | Chloroquine diphosphate | CHIR-99021 (CT99021) | MK-2206 2HCl | Dorsomorphin dihydrochloride

DATA ITEMS CITED :

26

MOLECULAR FORMULA :

C20-H24-N2-O-S

MOLECULAR WEIGHT :

340.52

WISWESSER LINE NOTATION :

T C666 BS IVJ D1 GM2N2&2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

56 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

400 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

DNA inhibition

TYPE OF TEST :

Mutation test systems - not otherwise specified

MUTATION DATA

TYPE OF TEST :

DNA adduct

TEST SYSTEM :

Mammal - species unspecified Lymphocyte

DOSE/DURATION :

6 umol/L

REFERENCE :

PMSBA4 Progress in Molecular and Subcellular Biology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.1- 1969- Volume(issue)/page/year: 2,232,1971