The association of vitamins C and K3 kills cancer cells mainly by autoschizis, a novel form of cell death. Basis for their potential use as coadjuvants in anticancer therapy

Verrax, Julien; Cadrobbi, Julie; Delvaux, Marianne; Jamison, James M.; Gilloteaux, Jacques; Summers, Jack L.; Taper, Henryk; Calderón, Pedro Buc

doi:10.1016/s0223-5234(03)00082-5

Cited by 71 publications

(46 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Electrophoresis of DNA revealed a spread pattern. These results in conjunction with previous studies (Buc Calderon et al, 2003;Verrax et al, 2003Verrax et al, , 2004Jamison et al, 2005) suggested that Ca 2ϩ disregulation and cell acidification led to the caspase-3-independent serial reactivation of DNase I and DNase II and the degradation of T24 cell DNA ).…”

Section: Cytotoxicity Of Vc:vk 3 Combinationsupporting

confidence: 86%

“…*Based on this report, Gilloteaux et al, 1998aGilloteaux et al, , 2001aGilloteaux et al, , 2001bGilloteaux et al, , 2001cGilloteaux et al, , 2003aGilloteaux et al, , 2003bGilloteaux et al, , 2004Gilloteaux et al, , 2005Venugopal et al, 1996b, Calderon et al, 2003Jamison et al, 2004;Verrax et al, 2003Verrax et al, , 2004. Necrosis results from a variety of accidental cytocidal actions.…”

Section: Cytotoxicity Of Vc:vk 3 Combinationmentioning

confidence: 98%

“…Cells in G 1 during vitamin treatment arrested in G 1 while those in S-phase progressed through S-phase and arrested in G 2 /M. The fact that catalase treatment abrogated both cell cycle arrest and cell death implicated H 2 O 2 in these processes (Venugopal et al, 1996a(Venugopal et al, , 1996bBuc Calderon et al, 2002;Verrax et al, 2003). Redox cycling of VC and VK 3 increased H 2 O 2 production and decreased cellular thiol levels and DNA content, while increasing intracellular Ca 2ϩ levels and lipid peroxidation.…”

Section: Cytotoxicity Of Vc:vk 3 Combinationmentioning

confidence: 99%

“…Subsequently, autoschizis has been observed in a variety of cell lines, including renal carcinoma (Caki-1) (Arnold et al, 1999), ovarian carcinoma (MDAH 2774) (Gilloteaux et al, 1999b(Gilloteaux et al, , 2003a(Gilloteaux et al, , 2003b, and murine prostatic carcinoma (TRAMP) , as well as in vivo . A number of independent laboratories have also reported observing autoschizic cell death (Buc Calderon et al, 2002;Verrax et al, 2003Verrax et al, , 2004Levanon 2004). Finally, based on previous publications and this one, "autoschizis" would become a new cell biology term (proposed to Federative Committee of Anatomical Terminology) that describes a dynamic mechanism of cell self-excision observed in normal cell [in erythropoiesis (reticulocyte formation), spermatocytogenesis (spermatid seceding from their cytoplasmic bodies), etc.]…”

mentioning

confidence: 97%

See 3 more Smart Citations

Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

Gilloteaux¹,

Jamison²,

Arnold³

et al. 2005

Anat. Rec.

Self Cite

View full text Add to dashboard Cite

Feulgen and actin-phalloidin staining as well as gel electrophoresis have been employed in conjunction with cell ultrastructure to describe the effects of 1-, 2-, and 4-hr ascorbate (VC), menadione (VK 3 ), and ascorbate:menadione (VC:VK 3 ) treatments on the T24 human bladder carcinoma cell line. T24 cells exposed to VC alone display blebs and other superficial membrane defects related to membrane alterations and to superficial cytoskeleton changes. VK 3 treatment damages the cell nucleus and organelles, leads to the redistribution of the organelles in the perikaryon as a consequence of cytoskeletal damage, and results in cytoplasmic self-excisions. After VC:VK 3 treatment, the cells show exaggerated alterations characteristic of each vitamin treatment alone, including damaged mitochondria, self-excision of organelle-free pieces of cytoplasm, and extrusion of the perikaryon containing a nucleus surrounded by the damaged organelles. The nuclear envelope appears intact and contains chromatin that decondenses and dissipates. During the cellular demise that concludes with apparent karyolysis, the cells significantly decrease their size and alter their shape. However, the cisterns of rough endoplasmic reticulum are undamaged, but may become dilated. Since the cellular phenomena leading to cell death differ morphologically from apoptosis and necrosis, but entail selfcutting without nuclear bodies, this new form of cell death was called autoschizis. In addition, gel electrophoresis and Feulgen staining demonstrate that autoschizis is accompanied by random DNA degeneration.

show abstract

Section: Cytotoxicity Of Vc:vk 3 Combinationsupporting

confidence: 86%

Section: Cytotoxicity Of Vc:vk 3 Combinationmentioning

confidence: 98%

Section: Cytotoxicity Of Vc:vk 3 Combinationmentioning

confidence: 99%

mentioning

confidence: 97%

See 2 more Smart Citations

Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

Gilloteaux¹,

Jamison²,

Arnold³

et al. 2005

Anat. Rec.

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has been shown that vitamins K1, K2 and K3 could inhibit the growth of various rodent-and human-derived neoplastic cell lines in vitro, such as oral epidermal cancer, nasopharyngeal cancer, breast cancer, leukemia and hepatocellular carcinoma (HCC) cell lines (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). In marked contrast to numerous reports demonstrating in vitro antitumor effects of vitamin K, there are few reports demonstrating in vivo antitumor effects of vitamin K. Furthermore, it has not been examined so far whether vitamin K induces antitumor effects on CRC.…”

Section: Introductionmentioning

confidence: 99%

Vitamins K2, K3 and K5 exert antitumor effects on established colorectal cancer in mice by inducing apoptotic death of tumor cells

Ogawa¹,

Nakai²,

Deguchi³

et al. 2007

Int J Oncol

View full text Add to dashboard Cite

Abstract. Although a number of studies have shown that vitamin K possesses antitumor activities on various neoplastic cell lines, there are few reports demonstrating in vivo antitumor effects of vitamin K, and the antitumor effect on colorectal cancer (CRC) remains to be examined. Therefore, antitumor effects of vitamin K on CRC were examined both in vitro and in vivo. Vitamins K2, K3 and K5 suppressed the proliferation of colon 26 cells in a dose-dependent manner, while vitamin K1 did not. On flow cytometry, induction of apoptosis by vitamins K2, K3 and K5 was suggested by population in sub-G1 phase of the cell cycle. Hoechst 33342 staining and a twocolor flow cytometric assay using fluorescein isothiocyanateconjugated annexin V and propidium iodide confirmed that vitamins K2, K3 and K5 induced apoptotic death of colon 26 cells. Enzymatic activity of caspase-3 in colon 26 cells was significantly up-regulated by vitamins K2, K3 and K5. The pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Aspfluoromethyl ketone, substantially prevented vitamin Kmediated apoptosis. In vivo study using syngeneic mice with subcutaneously established colon 26 tumors demonstrated that intravenous administration of vitamins K2, K3 and K5 significantly suppressed the tumor growth. The number of apoptotic tumor cells was significantly larger in the vitamin K-treated groups than in the control group. These results suggest that vitamins K2, K3 and K5 exerted effective antitumor effects on CRC in vitro and in vivo by inducing caspasedependent apoptotic death of tumor cells, suggesting that these K vitamins may be promising agents for the treatment of patients with CRC. IntroductionWorldwide, colorectal cancer (CRC) ranks third in cancer incidence after lung and breast, and is a major cause of cancer mortality (1). In 2000, there were 943,000 new cases diagnosed and 510,000 deaths worldwide, corresponding figures for Europe were 363,000 cases and 199,000 deaths (2). Although surgery alone is the standard approach in localized malignancy, approximately 50% of early-stage patients present disease relapse (3). Furthermore, approximately 30% of CRC is diagnosed when it is already at an advanced stage. There are also a considerable number of patients who cannot undergo surgery even at an early stage of the disease due to severe complications, such as chronic heart failure, chronic renal failure and chronic obstructive pulmonary diseases. Fluoropyrimidine-based chemotherapy is now considered the standard treatment for patients with inoperable CRC, but approximately 90% of patients do not respond to chemotherapy based on 5-fluorouracil (5-FU)/folinic acid (4). Thus, the development of new treatment modalities is necessary to improve the overall survival rate of patients with CRC.Vitamin K is an essential vitamin that was discovered as a fat-soluble anti-hemorrhagic agent. Vitamin K is also known as an obligatory cofactor in the post-translational γ-carboxylation of glutamic acid residues (5-8). Vitamin K-dependent proteins include prothrombin (fact...

show abstract

Autoschizis: A Mode of Cell Death of Cancer Cells Induced by a Prooxidant TreatmentIn VitroandIn Vivo

Gilloteaux

Jamison

Arnold³

et al. 2018

Apoptosis and Beyond

View full text Add to dashboard Cite

The association of vitamins C and K3 kills cancer cells mainly by autoschizis, a novel form of cell death. Basis for their potential use as coadjuvants in anticancer therapy

Cited by 71 publications

References 34 publications

Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

Vitamins K2, K3 and K5 exert antitumor effects on established colorectal cancer in mice by inducing apoptotic death of tumor cells

Autoschizis: A Mode of Cell Death of Cancer Cells Induced by a Prooxidant TreatmentIn VitroandIn Vivo

Contact Info

Product

Resources

About