The activity of caspases in spontaneous and camptothecin-induced death of melanotic and amelanotic melanoma cell

Cichorek, M; Kozłowska, K; Bryl, Ewa

doi:10.4161/cbt.6.3.3701

Cited by 18 publications

(23 citation statements)

References 35 publications

(74 reference statements)

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“…The results for cells of both melanoma lines, obtained after 4 hours of incubation, may indicate the contribution of the Fas/FasL system to the induction of spontaneous apoptosis, though only to an insignificant degree (only a few per cent). So, we can say that apoptosis, induced by the Fas/FasL system, does not play a key role in transplantable melanoma cells [20,30], despite the higher ability to undergo spontaneous apoptosis of melanotic melanoma cells in comparison with amelanotic melanoma cells -more aggressive and with a lower ability to spontaneous apoptosis. Thus, we can suggest that in both transplantable melanoma cell lines the intrinsic pathway of apoptosis plays a more important role than the extrinsic one [18,30].…”

Section: Discussionmentioning

confidence: 99%

Fas and FasL expression on cells of two transplantable melanoma lines according to their different biological properties.

Zielińska

Kozłowska²,

Cichorek³

et al. 2008

Folia Histochem Cytobiol.

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Abstract. Fas and FasL interaction induces apoptotic cell death. In immunocompetent cells it plays a crucial role in the effector functions of the cells and in the regulation of host immune response. In tumours (e.g. melanoma), FasL expression possibly counteracts the Fas-positive effector T cells that infiltrate into tumours, and consequently the Fas/FasL interaction can contribute to the escape of tumour cells from the systemic immune response. In this study we examined differences in Fas and FasL expression on cells from the hamster melanotic melanoma line (Ma) and a more aggressive amelanotic melanoma line (Ab). We also tried to find out whether the Fas/FasL expression induces an ability to undergo spontaneous apoptosis in these two transplantable melanoma lines. Our previous studies have shown that cells of the Ma line have a higher ability to undergo spontaneous apoptosis than cells of the Ab line. Isolated transplantable melanoma cells were incubated for 4 and 24 hours and after that time the expression of Fas and FasL was estimated by flow cytometry. The results show that there was no Fas expression, although FasL was detected on both melanoma cell lines. Therefore the data reported by other authors indicate that a lack or a low level of Fas expression and an ectopic expression of FasL on melanoma cells can be an escape mechanism of the tumour, to avoid host immune responses. The content of FasL-positive melanotic melanoma cells was higher than in amelanotic melanoma cells and increased with the prolongation of the incubation time. FasL expression on amelanotic melanoma cells was detected after 24 hours at a level similar to that on melanotic melanoma cells after 4 hours incubation time. FasL expression on melanoma cells can induce apoptosis in cytotoxic T lymphocytes and NK cells which are responsible for tumour cells elimination. The results obtained suggest that the Fas/FasL system does not play any significant role in spontaneous apoptosis of two melanoma cell lines. But these results may indicate the presence of immune privilege of tumour cells with FasL expression.

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Section: Discussionmentioning

confidence: 99%

Fas and FasL expression on cells of two transplantable melanoma lines according to their different biological properties.

Zielińska

Kozłowska²,

Cichorek³

et al. 2008

Folia Histochem Cytobiol.

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“…In addition, the same combination of drugs was also shown to induce apoptosis despite the fact that its extent was significantly lower in mutant p53 cells. CPTs and etoposide have been shown to induce p53-dependent mitochondrial apoptosis, with strong involvement of caspases [19,23,24]. Still, p53-independent death has also been associated with topoisomerase inhibitors [25] and it appears that several other mechanisms are involved in both processes as individual agents might interfere with other stress signaling pathways and/or directly with some organelles such as mitochondria as has been demonstrated in human gastric cancer cells [26] and cervical cancer cells [27].…”

Section: Discussionmentioning

confidence: 97%

“…To this end, topoisomerase inhibiting agents alone or in combination with other antineoplastics have been found to exert antiproliferative effects against malignant melanocytes [19,20] despite the fact that selective resistance against them may develop in the same cells [21]. Since the expression of individual topoisomerases in melanoma may vary [14] in addition to often aberrant function of p53-dependent pathway which is mostly targeted by topoisomerase inhibitors [2], concerted suppression of topoisomerase I and II in the same cells may be perspective in enhancing cytotoxicity and proapoptic response while overcoming aforementioned obstacles.…”

Section: Discussionmentioning

confidence: 99%

Dual inhibition of topoisomerases enhances apoptosis in melanoma cells

Rudolf¹,

Červinka²,

Rudolf³

2010

neo

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The cytotoxicity of topoisomerase I inhibiting camptothecin, topoisomerase II inhibiting etoposide and their combination were investigated in wild type p53 Bowes and mutant p53 SK-MEL-28 melanoma cell lines during 24h. A combination of camptothecin and etoposide (1 μg/ml + 10 μg/ml) proved to be efficient in both types of cell lines, although mutant p53 cells exhibited a higher resistance. Further studies proved that in Bowes cells, a combination of drugs induced p53-dependent mitochondrial apoptosis characterized by activation of caspases-8 and -2, -9 and -3 with some concurrent involvement of oxidative stress. In SK-MEL-28 cells, apoptosis was found to be mediated via increased oxidative stress, activation of stress kinases such as p38 and SAPK/JNK and mitochondrial dysfunction without significant involvement of p53 and its transactivated target genes. These results demonstrate efficiency of dual inhibition of topoisomerases in melanoma cells with functional as well as mutant p53 and point out at possible further investigation of this modality in preclinical and clinical oncology.

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“…Melanoma cells were isolated for each experiment from solid tumors by a non-enzymatic method described earlier [13]. The suspension consisted of 95 -98% viable cells (estimated by trypan blue test).…”

Section: Methodsmentioning

confidence: 99%

“…In our hamster's melanoma model (Bomirski melanomas) camptothecin caused death of amelanotic melanoma cells (Ab line) through the apoptotic way while melanotic melanoma cells (Ma line) were insensitive to the action of this substance [13,14]. These two transplantable melanoma lines, except the presence (Ma line) or lack (Ab line) of melanin, differ in many biological features e.g.…”

mentioning

confidence: 94%

Camptothecin-induced death of amelanotic and melanotic melanoma cells in different phases of cell cycle

Cichorek¹

2011

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Camptothecin and its analogues are used as S-phase specific antitumor drugs because of topoisomerase I inhibition providing cells to death by apoptosis. Our previous works documented that amelanotic hamster's melanoma is very sensitive to camptothecin. Because of the challenges in treating melanoma and S-phase specificity of camptothecin, we performed a study to search what melanoma cell cycle phases are susceptible to this substance.Melanotic (Ma) and amelanotic (Ab) lines of Bomirski hamster's melanoma were used. Camptothecin cytotoxicity was determined by TUNEL method and cell cycle analysis was done by DNA staining with propidium iodide.Camptothecin after short time killed amelanotic melanoma cells from S/G2/M phases but with extended time dying cells came from G0/G1. Melanotic melanoma had fewer cells in S/G2/M phases and 3-fold more of these cells spontaneously died in comparison to more aggressive amelanotic line. High susceptibility of amelanotic melanoma cells to camptothecin show that not only cells with proliferative activity were sensitive to this alkaloid but with extended time it killed cells from all cycle phases. High number of cells in S/G2/M phases and low rate of spontaneous death among amelanotic melanoma cells suggest that the expansive growth of this melanoma line depends mainly on the decreased ability to undergo spontaneous apoptosis. If the sensitivity of amelanotic melanoma is not only hamster's but also human melanoma feature, we can suspect that by choosing melanoma form for treatment with camptothecin we could improve effectiveness of this drug against melanoma.

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The activity of caspases in spontaneous and camptothecin-induced death of melanotic and amelanotic melanoma cell

Cited by 18 publications

References 35 publications

Fas and FasL expression on cells of two transplantable melanoma lines according to their different biological properties.

Fas and FasL expression on cells of two transplantable melanoma lines according to their different biological properties.

Dual inhibition of topoisomerases enhances apoptosis in melanoma cells

Camptothecin-induced death of amelanotic and melanotic melanoma cells in different phases of cell cycle

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