Ultrastructural Aspects Of Autoschizis: A New Cancer Cell Death Induced By The Synergistic Action Of Ascorbate/menadione On Human Bladder Carcinoma Cells
2-methyl-1; 4-naphthoquinone; antitumor-activity; apoptosis; autoschizis; bladder tumor; cell death; combined vitamin-c; cultured-mammalian-cells; growth-invitro; induced oxidative stress; Microscopy; necrosis; Pathology; scanning electron-microscopy; T24 ultrastructure; tumor; vitamins
Gilloteaux J; Jamison J M; Arnold D; Taper H S; Summers J L
Ultrastructural Pathology
2001
2001-05
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1080/019131201300343810" target="_blank" rel="noreferrer noopener">10.1080/019131201300343810</a>
Paclitaxel-Hyaluronic NanoConjugates Prolong Overall Survival in a Preclinical Brain Metastases of Breast Cancer Model
stem-cells; in-vivo; Oncology; central-nervous-system; lipid rafts; antitumor-activity; multidrug-resistance; acid-paclitaxel; cd44 expression; p-glycoprotein; targeted drug-delivery
Brain (central nervous system; CNS) metastases pose a life-threatening problem for women with advanced metastatic breast cancer. It has recently been shown that the vasculature within preclinical brain metastasis model markedly restricts paclitaxel delivery in approximately 90% of CNS lesions. Therefore to improve efficacy, we have developed an ultra-small hyaluronic acid (HA) paclitaxel nanoconjugate (similar to 5 kDa) that can passively diffuse across the leaky blood-tumor barrier and then be taken up into cancer cells (MDA-MB-231Br) via CD44 receptor-mediated endocytocis. Using CD44 receptor-mediated endocytosis as an uptake mechanism, HA-paclitaxel was able to bypass p-glycoprotein-mediated efflux on the surface of the cancer cells. In vitro cytoxicity of the conjugate and free paclitaxel were similar in that they (i) both caused cell-cycle arrest in the G(2)-M phase, (ii) showed similar degrees of apoptosis induction (cleaved caspase), and (iii) had similar IC50 values when compared with paclitaxel in MTT assay. A preclinical model of brain metastases of breast cancer using intracardiac injections of Luc-2 transfected MDA-MB-231Br cells was used to evaluate in vivo efficacy of the nanoconjugate. The animals administered with HA-paclitaxel nanoconjugate had significantly longer overall survival compared with the control and the paclitaxel-treated group (P < 0.05). This study suggests that the small molecular weight HA-paclitaxel nanoconjugates can improve standard chemotherapeutic drug efficacy in a preclinical model of brain metastases of breast cancer. (C) 2013 AACR.
Mittapalli R K; Liu X L; Adkins C E; Nounou M I; Bohn K A; Terrell T B; Qhattal H S; Geldenhuys W J; Palmieri D; Steeg P S; Smith Q R; Lockman P R
Molecular Cancer Therapeutics
2013
2013-11
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1158/1535-7163.mct-13-0132" target="_blank" rel="noreferrer noopener">10.1158/1535-7163.mct-13-0132</a>
The association of vitamins C and K-3 kills cancer cells mainly by autoschizis, a novel form of cell death. Basis for their potential use coadjuvants in anticancer therapy
antitumor-activity; ascorbic-acid; autoschizis; cancer; chemotherapy; dna; factor-kappa-b; fragmentation; induced apoptosis; lines; oxidative stress; Pharmacology & Pharmacy; pretreatment; tumor-cells; vitamins C and K-3
`Deficiency of alkaline and acid DNase is a hallmark in all non-necrotic cancer cells in animals and humans. These enzymes are reactivated at early stages of cancer cell death by vitamin C (acid DNase) and vitamin K-3 (alkaline DNase). Moreover, the coadministration of these vitamins (in a ratio of 100:1, for C and K-3, respectively) produced selective cancer cell death. Detailed morphological studies indicated that cell death is produced mainly by autoschizis, a new type of cancer cell death. Several mechanisms are involved in such a cell death induced by CK3, they included: formation of H2O2 during vitamins redox cycling, oxidative stress, DNA fragmentation, no caspase-3 activation, and cell membrane injury with progressive loss of organelle-free cytoplasm. Changes in the phosphorylation level of some critical proteins leading to inactivation of NF-kappaB appear as main intracellular signal transduction pathways. The increase knowledge in the mechanisms underlying cancer cells death by CK3 may ameliorate the techniques of their in vivo administration. The aim is to prepare the introduction of the association of vitamins C and K-3 into human clinics as a new, non-toxic adjuvant cancer therapy. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
Verrax J; Cadrobbi J; Delvaux M; Jamison J M; Gilloteaux J; Summers J L; Taper H S; Calderon P B
European Journal of Medicinal Chemistry
2003
2003-05
Journal Article
<a href="http://doi.org/10.1016/s0223-5234(03)00082-5" target="_blank" rel="noreferrer noopener">10.1016/s0223-5234(03)00082-5</a>