Divergent effect of taxol on proliferation, apoptosis and nitric oxide production in MHH225 CD34 positive and U937 CD34 negative human leukaemia cells

Alalami, O; Sammons, J.; Martin, Noreen; Hassan, H. T.

doi:10.1016/s0145-2126(98)00092-7

Cited by 16 publications

(7 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies showed the efficacy of taxanes on human leukemic cell lines (16,(19)(20)(21), as well as their effectiveness in inducing apoptosis in vivo (22) and in fresh leukemia cells in primary cultures (23). However, to the best of our knowledge, there is no report on the effect of paclitaxel on leukemia induced by virus.…”

Section: Discussionmentioning

confidence: 99%

“…In the clinic, paclitaxel has been widely used in several malignant solid tumors, such as ovarian cancer, breast cancer and lung cancer (15). However, a poor level of in vivo induction of apoptosis was achieved during a phase I clinical study with paclitaxel therapy in 26 leukemia patients (16). In addition, paclitaxel has a significantly weaker cytotoxic effect on CD34 positive AML cells than CD34 negative leukemia cell lines, such as HL-60 and U937 (16).…”

Section: Introductionmentioning

confidence: 99%

“…However, a poor level of in vivo induction of apoptosis was achieved during a phase I clinical study with paclitaxel therapy in 26 leukemia patients (16). In addition, paclitaxel has a significantly weaker cytotoxic effect on CD34 positive AML cells than CD34 negative leukemia cell lines, such as HL-60 and U937 (16). Considering the fact that leukemia is a heterogeneous disease with different cell types and immune phenotypes, it is necessary to investigate the effect of paclitaxel on different types of leukemia cell lines.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Different regulatory pathways are involved in the proliferative inhibition of two types of leukemia cell lines induced by paclitaxel

et al. 2013

View full text Add to dashboard Cite

Abstract. Paclitaxel, one of the broadest-spectrum anticancer agents, is currently being used in the treatment of patients with solid tumors. In the present study, we compared the effect of paclitaxel on two types of leukemia cells. Our results showed that paclitaxel could inhibit the proliferation of MEL and K562 cells in a dose-and time-dependent manner. The mechanism of proliferative inhibition in K562 cells treated by paclitaxel was related to the cell cycle arrest in the G 2 /M phase, as well as the induction of apoptosis. By contrast, MEL cells treated by paclitaxel showed significant characteristics of necrosis, which indicated that the mode of cell death induced by paclitaxel in these two types of leukemia cells differed. Advances in research of the cell cycle, apoptosis and necrosis will extend our understanding of the mechanisms of paclitaxel-induced cell death, particularly in leukemia cells. Further elucidation of the mechanisms of necrosis in MEL cells may expedite the development of improved paclitaxel-based regimens for cancer therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Different regulatory pathways are involved in the proliferative inhibition of two types of leukemia cell lines induced by paclitaxel

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Antimicrotubule agents are known to induce phosphorylation and thus inactivation of the antiapoptotic members of the Bcl family such as Bcl-2 [7], [8]. The efficacy of taxanes on human leukemic cell lines [9], [10] as well as their effectiveness in inducing apoptosis in vivo [11] and in fresh leukemia cells in primary cultures [12] have been investigated. Al Alami et al have demonstrated the dose-dependency and time-dependency of the anti-tumor effects of paclitaxel in leukemia [9].…”

Section: Introductionmentioning

confidence: 99%

“…The efficacy of taxanes on human leukemic cell lines [9], [10] as well as their effectiveness in inducing apoptosis in vivo [11] and in fresh leukemia cells in primary cultures [12] have been investigated. Al Alami et al have demonstrated the dose-dependency and time-dependency of the anti-tumor effects of paclitaxel in leukemia [9]. Anti-leukemic activity of taxanes was studied in samples with chromosomal abnormalities associated with an unfavorable outcome, such as the Bcr-Abl translocation (Philadelphia chromosome) [13].…”

Section: Introductionmentioning

confidence: 99%

Long Circulating Lectin Conjugated Paclitaxel Loaded Magnetic Nanoparticles: A New Theranostic Avenue for Leukemia Therapy

2011

View full text Add to dashboard Cite

Amongst all leukemias, Bcr-Abl positive chronic myelogenous leukemia (CML) confers resistance to native drug due to multi drug resistance and also resistance to p53 and fas ligand pathways. In the present study, we have investigated the efficacy of microtubule stabilizing paclitaxel loaded magnetic nanoparticles (pac-MNPs) to ascertain its cytotoxic effect on Bcr-Abl positive K562 cells. For active targeted therapy, pac-MNPs were functionalized with lectin glycoprotein which resulted in higher cellular uptake and lower IC50 value suggesting the efficacy of targeted delivery of paclitaxel. Both pac-MNPs and lectin conjugated pac-MNPs have a prolonged circulation time in serum suggesting increased bioavailability and therapeutics index of paclitaxel in vivo. Further, the molecular mechanism pertaining to pac-induced cytotoxicity was analyzed by studying the involvement of different apoptotic pathway proteins by immunoblotting and quantitative PCR. Our study revealed simultaneous activation of JNK pathway leading to Bcr-Abl instability and the extrinsic apoptotic pathway after pac-MNPs treatment in two Bcr-Abl positive cell lines. In addition, the MRI data suggested the potential application of MNPs as imaging agent. Thus our in vitro and in vivo results strongly suggested the pac-MNPs as a future prospective theranostic tool for leukemia therapy.

show abstract

Late apoptotic effects of taxanes on K562 erythroleukemia cells: Apoptosis is delayed upstream of caspase‐3 activation

Gangemi

Santamaria

Bargellesi

et al. 2000

Intl Journal of Cancer

View full text Add to dashboard Cite

The efficacy of taxanes on human leukemia cells is the object of intensive in vitro investigation concerning the influence of cell‐type‐specific characteristics on cytotoxic response to drugs. The present study dissects the response to taxanes of HL60 acute myelomonocytic leukemia and of K562 chronic myelogenous leukemia, in parallel over a 72‐hr time‐span. The kinetics of cytotoxicity following pulsed and continuous exposure to either taxol or taxotere showed a delayed response of K562 cells independently of dose and type of exposure. In K562 cells, apoptosis became evident at 48 hr and prominent at 72 hr of treatment. These events were mirrored by delayed kinetics of caspase‐3 activation. Comparable microtubule targeting was demonstrated in HL60 and in K562 cell lines, as bcl‐2 and raf‐1 were phosphorylated following treatment with taxanes. These observations indicate that early activation processes were responsible for apoptosis, but that the delay was determined by other factors. In addition, cell‐free‐system experiments excluded the presence of excess nuclear and/or cytoplasmic inhibitory factors and demonstrated that K562 cells possess a fully competent caspase system which can be readily activated. Processing of caspase‐3 pro‐enzyme was in fact increased by addition of cytochrome c. These results extend to taxol and taxotere the notion that drug‐induced apoptosis is delayed upstream of caspase‐3 activation in K562 cells, that such kinetics is independent of drug concentration and exposure time, and that it is linked to intrinsic cellular characteristics mapping between bcl‐2 phosphorylation and cytochrome c release. Int. J. Cancer 85:527–533, 2000. © 2000 Wiley‐Liss, Inc.

show abstract

Divergent effect of taxol on proliferation, apoptosis and nitric oxide production in MHH225 CD34 positive and U937 CD34 negative human leukaemia cells

Cited by 16 publications

References 26 publications

Different regulatory pathways are involved in the proliferative inhibition of two types of leukemia cell lines induced by paclitaxel

Different regulatory pathways are involved in the proliferative inhibition of two types of leukemia cell lines induced by paclitaxel

Long Circulating Lectin Conjugated Paclitaxel Loaded Magnetic Nanoparticles: A New Theranostic Avenue for Leukemia Therapy

Late apoptotic effects of taxanes on K562 erythroleukemia cells: Apoptosis is delayed upstream of caspase‐3 activation

Contact Info

Product

Resources

About