The role of the intrinsic FAS pathway in Titanocene Y apoptosis: The mechanism of overcoming multiple drug resistance in malignant leukemia cells

Kater, Lisa; Claffey, James; Hogan, Megan; Jesse, Patrick; Kater, Benjamin; Strauss, Susanne; Tacke, Matthias; Prokop, Aram

doi:10.1016/j.tiv.2011.09.010

Cited by 21 publications

(13 citation statements)

References 22 publications

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“…Those results clearly point to apoptosis as the principal mode of cell death in Caki-1 cells treated with oximato titanocene compounds 2b and 2c . Other titanocenes like TDC, Titanocene C (bis-[N,N-dimethylamino-2(N-methylpyrrolyl)-methyl-cyclopentadienyl]titanium(IV) dichloride), X ([1,2-di(cyclopentadienyl)-1,2-di-(4-N,N-dimethylaminophenyl)ethanediyl]titanium(IV) dichloride) and Y, and heterometallic complexes containing titanocene fragments are also known to induce apoptosis in different cancer cell lines [16,21,27,30,94,95]. Moreover, as shown in Figure 7, compound 2c in a concentration 6 times lower than that of cisplatin and Titanocene Y (one of the benchmarks for activity in Caki-1 cancer cells and tumours) reduces the viability of cells in a much higher percentage and is more apoptotic.…”

Section: Resultsmentioning

confidence: 99%

Novel enantiopure cyclopentadienyl Ti(IV) oximato compounds as potential anticancer agents

Cueva-Alique

Muñoz-Moreno

Benabdelouahab

et al. 2016

Journal of Inorganic Biochemistry

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The synthesis and characterization of new enantiopure cyclopentadienyl titanium oximato compounds (S,R)-[(η5-C5H5)Ti{κ2NO,(R)NH·HCl}Cl2] (R = Ph (phenyl) 1a·HCl, Bn (benzyl) 1b·HCl, 2-pic (2-picolyl) 1c·HCl), (S,R)-[(η5-C5H5)TiCl2{κ2NO,(Ph)NH}] (1a) and (S,R)-[(η5-C5H5)2TiCl{κ2NO,(R)NH}] (R = Ph 2a, Bn 2b, 2-pic 2c), along with studies on their behaviour in D2O at different pD values are reported. The structure of previously described ammonium-oxime (2S,5R)-{NOH,(Bn)NH·HCl} (b·HCl) and novel titanium derivative 1a have been determined by single crystal X-ray crystallography. The effect of the compounds on cytotoxicity, cell adhesion and migration of the androgen-independent prostate cancer PC-3 cells has been assessed. Compounds 2b and 2c are more cytotoxic than additive doses of titanocene dichloride and free oxime proligand, probing the synergistic effect of these novel compounds. The cytotoxicity of 2b and 2c has been further evaluated against human renal Caki-1, colon DLD-1 and triple negative breast MDA-MB-231 cancer cell lines. The activity found for 2c on PC-3 and Caki-1 is higher than that of highly active Titanocene Y (bis-[(p-methoxybenzyl)cyclopentadienyl]titanium(IV) dichloride), while showing selectivity against renal cancer when compared to a non-tumorigenic human renal (HEK-293T) cell line. Compounds 2b and especially 2c are apoptotic in Caki-1 cancer cell lines. Cell adhesion and wound-healing assays confirmed that derivatives 1c·HCl, 2b and 2c affect the adhesion and migration patterns of the PC-3 cell line. Interactions of the novel compounds with plasmid (pBR322) DNA have also been studied, showing that the oximato Ti(IV) derivatives have a weak or no interaction with DNA at physiological pH.

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Section: Resultsmentioning

confidence: 99%

Novel enantiopure cyclopentadienyl Ti(IV) oximato compounds as potential anticancer agents

Cueva-Alique

Muñoz-Moreno

Benabdelouahab

et al. 2016

Journal of Inorganic Biochemistry

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“…Mechanisms underlying MDR include, among others, enhancement of drug efflux carried out by membrane proteins (e.g., P-gp, MRP, and LRP) [23], [24], reinforcement in enzymatic detoxification of cytotoxic drugs by glutathione-s-transferase system [25]–[27], and inhibition of cell apoptosis [28], [29]. The ‘classic’ MDR is mediated by P-gp [4], [30], [31].…”

Section: Discussionmentioning

confidence: 99%

Activated ERM Protein Plays a Critical Role in Drug Resistance of MOLT4 Cells Induced by CCL25

et al. 2013

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We have previously demonstrated that the CCR9/CCL25 signaling pathway plays an important role in drug resistance in human acute T-lymphocytic leukemia (T-ALL) by inducing activation of ERM protein with polarized distribution in T-ALL cell line MOLT4. However, the mechanism of action of the activated ERM protein in the drug resistance of MOLT4 cells induced by CCL25 remains uncharacterized. Here we investigated the mechanism of CCR9/CCL25-initiated drug resistance in CCR9-high-expressing T-ALL cells. Our results showed that 1) the function of P-gp was increased after treatment with CCL25; 2) P-gp colocalized and co-immunoprecipitated with p-ERM and F-actin in CCL25 treated cells; and 3) ERM-shRNA conferred drug sensitivity coincident with release of ERM interactions with P-gp and F-actin after treatment with CCL25. These data suggest it is pivotal that P-gp associate with the F-actin cytoskeleton through p-ERM in CCR9/CCL25 induced multidrug resistance of T-ALL cells. Strategies aimed at inhibiting P-gp-F-actin cytoskeleton association may be helpful in increasing the efficiency of therapies in T-ALL.

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“…On the other hand, Titanocene Y triggered apoptosis in leukemia cells, regardless of the expression of anti-apoptotic Bcl-2 and pro-apoptotic smac. Moreover, the titanium compounds are also effective against leukemia cells that are multidrug resistant due to overexpression of P-gp [30].…”

Section: Vanadocenesmentioning

confidence: 99%

Vanadium, Ruthenium and Copper Compounds: A New Class of Nonplatinum Metallodrugs with Anticancer Activity

León

Cadavid-Vargas²,

Virgilio³

et al. 2017

CMC

129

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Cancer is a group of diseases involving abnormal cell growth. The cells grow uncontrollably with the potential to invade and spread to other parts of the body. This disease is one of the principal death causes in the world, thus becoming a significant topic of scientific research. On the other hand, transition metals play a fundamental role in different living systems. In particular, Metallodrugs represent new and powerful tools for diverse therapeutic applications. To date, various metallodrugs display interesting biological activities for chemotherapy. In this field, cisplatin was the first inorganic compound with high relevance in cancer treatment. This compound was a leader agent in clinical use. Toxicity and resistance problems trigger the development of other platinum drugs with better clinical perspective and also raise the scientific interest for the putative antitumor properties of V, Ru and Cu compounds. Several scientific articles show that complexes of these metals are the new metal-based drugs used in the treatment of several cancers, such us, lung, colon, breast, bladder, etc. In this review we recapitulate current information and new advances on antitumor in vitro effects of several organic and inorganic compounds derived from copper, ruthenium and vanadium. These metal derived compounds targeting DNA or cell proteins involved in cell signaling pathways related to cancer. The mechanisms of cell death of these metallodrugs have also been comprehensibly reviewed. The knowledge of these mechanisms of death and the relationship between chemical structure and biological activity may be useful for the design of new metal-based drugs with promising pharmacologic applications as anticancer agents.

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The role of the intrinsic FAS pathway in Titanocene Y apoptosis: The mechanism of overcoming multiple drug resistance in malignant leukemia cells

Cited by 21 publications

References 22 publications

Novel enantiopure cyclopentadienyl Ti(IV) oximato compounds as potential anticancer agents

Novel enantiopure cyclopentadienyl Ti(IV) oximato compounds as potential anticancer agents

Activated ERM Protein Plays a Critical Role in Drug Resistance of MOLT4 Cells Induced by CCL25

Vanadium, Ruthenium and Copper Compounds: A New Class of Nonplatinum Metallodrugs with Anticancer Activity

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