Abstract:
:beta-Lapachone and certain of its derivatives directly bind and inhibit topoisomerase I (Topo I) DNA unwinding activity and form DNA-Topo I complexes, which are not resolvable by SDS-K+ assays. We show that beta-lapachone can induce apoptosis in certain cells, such as in human promyelocytic leukemia (HL-60) and human prostate cancer (DU-145, PC-3, and LNCaP) cells, as also described by Li et al. (Cancer Res., 55: 0000-0000, 1995). Characteristic 180-200-bp oligonucleosome DNA laddering and fragmented DNA-containing apoptotic cells via flow cytometry and morphological examinations were observed in 4 h in HL-60 cells after a 4-h, > or = 0.5 microM beta-lapachone exposure. HL-60 cells treated with camptothecin or topotecan resulted in greater apoptotic DNA laddering and apoptotic cell populations than comparable equitoxic concentrations of beta-lapachone, although beta-lapachone was a more effective Topo I inhibitor. beta-Lapachone treatment (4 h, 1-5 microM) resulted in a block at G0/G1, with decreases in S and G2/M phases and increases in apoptotic cell populations over time in HL-60 and three separate human prostate cancer (DU-145, PC-3, and LNCaP) cells. Similar treatments with topotecan or camptothecin (4 h, 1-5 microM) resulted in blockage of cells in S and apoptosis. Thus, beta-lapachone causes a block in G0/G1 of the cell cycle and induces apoptosis in cells before, or at early times during, DNA synthesis. These events are p53 independent, since PC-3 and HL-60 cells are null cells, LNCaP are wild-type, and DU-145 contain mutant p53, yet all undergo apoptosis after beta-lapachone treatment. Interestingly, beta-lapachone treatment of p53 wild type-containing prostate cancer cells (i.e., LNCaP) did not result in the induction of nuclear levels of p53 protein, as did camptothecin-treated cells. Like other Topo I inhibitors, beta-lapachone may induce apoptosis by locking Topo I onto DNA, blocking replication fork movement, and inducing apoptosis in a p53-independent fashion. beta-Lapachone and its derivatives, as well as other Topo I inhibitors, have potential clinical utility alone against human leukemia and prostate cancers.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Planchon SM,Wuerzberger S,Frydman B,Witiak DT,Hutson P,Church DR,Wilding G,Boothman DAsubject
Has Abstractpub_date
1995-09-01 00:00:00pages
3706-11issue
17eissn
0008-5472issn
1538-7445journal_volume
55pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Neuroblastoma, one of the most common pediatric solid tumors, is characterized by two extreme disease courses, spontaneous regression and life-threatening progression. Here, we conducted a genome-wide search for differences in DNA methylation that distinguish between neuroblastomas of the two types. Three CpG islands ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2005-02-01 00:00:00
abstract::The importance of invasion in the complex process of metastasis, although now well established, has been studied with increasing molecular detail due to the development of robust in vitro experimental assays. In this issue of Cancer Research, we highlight a paper published by George Poste and colleagues that compared ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-0550
更新日期:2016-04-01 00:00:00
abstract::In normal tissues, the steady-state level of CD44 mRNA is low, and the variety of alternatively spliced transcripts produced by this complex gene is limited. Conversely, increased and disorderly expression of this gene has been observed in a number of types of cancer. This study analyzed the order in which the CD44 va...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract::The pancreatic carcinogen N-nitrosobis(2-oxopropyl)-amine was administered to Syrian golden hamsters after cholecystoduodenostomy and choledochostomy to investigate a possible bile reflux mechanism as a factor in pancreatic carcinogenesis. The induced lesions were similar in morphology, multiplicity, and distribution ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-07-01 00:00:00
abstract::Successive B16 melanoma tumor lines were selected for their ability to form pulmonary tumor nodules. This was accomplished by injecting tumor cells i.v. into syngeneic C57BL/6 mice and 2 to 3 weeks later collecting the secondary tumor growths and placing them into tissue culture. These tumor cells were then injected i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-01-01 00:00:00
abstract::A monoclonal immunoglobulin M (IgM) antibody (38-13) which recognizes Burkitt's lymphoma (BL) cells, by reacting with the neutral glycolipid Gal alpha 1 leads to 4-Gal beta 1 leads to 4-Glc beta 1 leads to 1-ceramide, was recently characterized. This monoclonal IgM was coupled to either ricin A chain or gelonin. The t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::Two lines of human colonic carcinoma cells have different sensitivities to 5-fluorouracil and 1-(2-chlorethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU). The growth of the BE line is 50% inhibited by 330 microM 5-fluorouracil and 15 microM methyl-CCNU, and the HT-29 line is 50% inhibited by 85 and 140 microM,...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-12-01 00:00:00
abstract::Standardized and reproducible preclinical models that recapitulate the dynamics of prostate cancer are urgently needed. We established a bank of transplantable patient-derived prostate cancer xenografts that capture the biologic and molecular heterogeneity currently confounding prognostication and therapy development....
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-2921-T
更新日期:2014-02-15 00:00:00
abstract::Cultured explants of mouse mammary gland were investigated for their capacity to secrete a cathepsin B-like cysteine proteinase. This enzyme had been shown previously to be secreted excessively from cultured explants of human breast tumors and spontaneous mouse mammary carcinomas. We now show that secretion is also ob...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-05-01 00:00:00
abstract::The androgen receptor (AR) regulates gene transcription by binding to androgen response elements in target gene promoters. The prostate-specific antigen (PSA) gene has a polymorphic androgen response element sequence with two alleles, A and G. We hypothesize that allelic differences in AR-driven PSA expression may inf...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-02-15 00:00:00
abstract::The association of intrauterine exposure to diethylstilbestrol (DES) and the subsequent development of reproductive tract abnormalities in young women has been well documented. Although the incidence of vaginal adenocarcinoma was low in the exposed population, vaginal adenosis, a nonmalignant abnormality, was quite co...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-05-01 00:00:00
abstract::The sensitivity of the human promyelocytic cell line HL60 to killing by the lysosomotropic detergent N-dodecyl imidazole (C12-Im) has been investigated in the exponential and stationary growth states and before and after differentiation induced by suitable effector molecules. Undifferentiated HL60 cells were more sens...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-02-01 00:00:00
abstract::In an effort to achieve high concentrations of 5-fluorouracil (5-FUra) in the hepatic circulation while minimizing systemic exposure, several routes of intrahepatic administration were compared in the canine model. To ascertain these data, 5-FUra (30 mg/kg) was given as a bolus into either a systemic vein (femoral vei...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
abstract::Ionizing radiation (IR) and concomitant angiostatin (AS) produce greater than additive local antitumor effects. We examined whether prolonged AS treatment added to IR reduces proliferation of lung metastases from LLC primary tumors. Flank tumors were treated with 40 Gy with or without AS (25 mg/kg/day). IR plus a 14-d...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-01-15 00:00:00
abstract::The possibility of decreasing the gastrointestinal (GI) toxic effects of 5-fluorouracil (5-FU) on the digestive tract such as its injury of cells and induction of diarrhea, without reducing its antitumor activity, was investigated in rats. Oxonic acid was found to inhibit the phosphorylation of 5-FU to 5-fluorouridine...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
abstract::The alternative reading frame (ARF) tumor suppressor exerts both p53-dependent and p53-independent activities critical to the prevention of cancer in mice and humans. Recent evidence from mouse models suggests that when p53 is absent, further loss of ARF can widen the tumor spectrum, and potentiate invasion and metast...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-1743
更新日期:2007-10-01 00:00:00
abstract::Recent evidence from our laboratory and from others suggested that pretreatment with alpha-difluoromethylornithine (DFMO) sensitizes some human and rodent tumor cell lines to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Many human tumor cells are resistant to chloroethylnitrosourea-induced DNA interstrand cross-linkin...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-09-01 00:00:00
abstract::KRAS-activating mutations drive human non-small cell lung cancer and initiate lung tumorigenesis in genetically engineered mouse (GEM) models. However, in a GEM model of KRAS(G12D)-induced lung cancer, tumors arise stochastically following a latency period, suggesting that additional events are required to promote ear...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-1249
更新日期:2015-12-15 00:00:00
abstract::The ING family of proteins is involved in the regulation of diverse processes ranging from cell cycle and cellular senescence to apoptosis. These effects are most likely through activation of acetylation-dependent pathways that ultimately alter gene expression. Despite reports linking ING to p53 activation, the molecu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-09-15 00:00:00
abstract::Metastatic prostate cancer continues to pose a difficult therapeutic challenge. Prostate cancer progression is associated with aberrant O-glycosylation of cancer cell surface receptors, but the functional impact of such events is uncertain. Here we report spontaneous metastasis of human prostate cancer xenografts that...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-0641
更新日期:2016-10-01 00:00:00
abstract::The role of dietary fat in cancer etiology is briefly discussed in terms of several major types of epidemiological evidence: geographic correlations, migrant studies, low-risk populations, and dietary modification trials. It appears that there is no conclusive evidence that lowering dietary fat intake will result in l...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-09-01 00:00:00
abstract::G3361/CP cells, a cisplatin (CDDP)-resistant subclone of the human melanoma cell line G3361, overexpress wild-type p53 protein and demonstrate an increase in the percentage of cells in G0--G1 arrest compared to parental cells. Exposing G3361/CP cells to human recombinant IFN-alpha2a reduces the high basal levels of p5...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-06-01 00:00:00
abstract::N'-[2-chloroethyl]-N[2-(methylsulfonyl) ethyl]-N'-nitrosourea (cystemustine),a chloroethylnitrosourea antineoplastic drug, provokes cellular proliferation inhibition and redifferentiation, but there was no cell death in B16 melanoma tumors. Because the phospholipid (Plp) metabolism is tightly involved in tumor growth ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-03-15 00:00:00
abstract::Frequent loss of heterozygosity (LOH) on the long arm of chromosome 5 (5q) has been reported in many types of human malignancies, including gastric carcinoma. One of the targets of 5q-LOH in colorectal carcinoma is certainly the adenomatous polyposis coli (APC) gene on 5q21. However, other evidence has suggested the p...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::Spontaneous tumorigenesis was evaluated in male p53-knockout (p53-/-) mice treated with dehydroepiandrosterone (DHEA), quercetin, d-limonene, or all-trans retinoic acid to determine whether tumor development in these mice can be modulated by cancer-chemopreventive agents. DHEA-treated mice experienced a delay in tumor...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-09-15 00:00:00
abstract::Brain tumors such as medulloblastoma (MB) and glioblastoma multiforme (GBM) can derive from neural precursors. For instance, many MBs are thought to arise from the uncontrolled proliferation of cerebellar granule neuron precursors (GNP). GNPs normally proliferate in early postnatal stages in mice but then they become ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-2249
更新日期:2010-02-01 00:00:00
abstract::Dendritic cells (DCs) need activation for the priming of antigen-specific immune responses. Recently activated DCs were described to prime in vitro strong T helper cell type 1 (Th(1)) responses, whereas at later time points, the same cells preferentially prime Th(2) cells [Langenkemp, A. et al., Nat. Immunol. 1: 311-3...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-07-01 00:00:00
abstract::Antibodies to formalin-fixed, syngeneic melanoma cells were prepared in mice, purified by immunoaffinity chromatography, and tested for binding activity to viable melanoma cells. The radiolabeled antibodies detected congruent to 9 X 10(6) melanoma antigenic sites/cell. The calculated average association constant (Ka) ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-08-01 00:00:00
abstract::By using the newly developed adhesive tumor cell culture system, we analyzed the chromosomal constitutions of primary lung tumor and nonmalignant normal lung tissue from 10 previously untreated patients with non-small cell lung cancer. Chromosomal analyses were successfully carried out in banded chromosome preparation...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::Bone marrow cells freshly aspirated from the 10 consecutive untreated adult patients with acute nonlymphocytic leukemia were cultured by 2 different methods: the conventional agar culture method for myeloid colony formation and its modification by daily feeding with culture medium. In 5 patients, colonies grew in much...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-12-01 00:00:00