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Sialic acid-binding lectin (leczyme) induces caspase-dependent apoptosis-mediated mitochondrial perturbation in Jurkat cells.

Tatsuta T, Hosono M, Sugawara S, Kariya Y, Ogawa Y, Hakomori S, Nitta K - Int. J. Oncol. (2013)

Bottom Line: The precise mechanisms of SBL-induced apoptotic signals were analyzed by combinational usage of specific caspase inhibitors and the mitochondrial membrane depolarization detector JC-1.It was demonstrated that SBL causes mitochondrial perturbation and the apoptotic signal is amplified by caspases and cell death is executed in a caspase-dependent manner.The efficacy of this combinational usage was shown for the first time, to distinguish the apoptotic pathway in detail.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan.

ABSTRACT
Sialic acid binding lectin (SBL) isolated from Rana catesbeiana oocytes is a multifunctional protein which has lectin activity, ribonuclease activity and antitumor activity. However, the mechanism of antitumor effects of SBL is unclear to date and the validity for human leukemia cells has not been fully studied. We report here that SBL shows cytotoxicity for some human leukemia cell lines including multidrug-resistant (MDR) cells. The precise mechanisms of SBL-induced apoptotic signals were analyzed by combinational usage of specific caspase inhibitors and the mitochondrial membrane depolarization detector JC-1. It was demonstrated that SBL causes mitochondrial perturbation and the apoptotic signal is amplified by caspases and cell death is executed in a caspase-dependent manner. The efficacy of this combinational usage was shown for the first time, to distinguish the apoptotic pathway in detail. SBL selectively kills tumor cells, is able to exhibit cytotoxicity regardless of P-glycoprotein expression and has potential as an alternative to conventional DNA-damaging anticancer drugs.

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Related in: MedlinePlus

Proposed model for apoptotic mechanism induced by SBL in Jurkat cells. SBL binds to cell surface and internalizes into tumor cells. SBL degrades cellular RNA and this ribotoxic stress triggers mitochondrial perturbation. Then, apoptotic signal is amplified by caspase activation leading to cell death.
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f8-ijo-43-05-1402: Proposed model for apoptotic mechanism induced by SBL in Jurkat cells. SBL binds to cell surface and internalizes into tumor cells. SBL degrades cellular RNA and this ribotoxic stress triggers mitochondrial perturbation. Then, apoptotic signal is amplified by caspase activation leading to cell death.

Mentions: SBL is a multifunctional protein which has lectin activity, ribonuclease activity and antitumor activity. The proposed mechanism of SBL-induced cell death is shown in Fig. 8. SBL binds to cell surface, internalizes into tumor cells and degrades cellular RNA and this ribotoxic stress triggers mitochondrial perturbation. The activation of p38 and JNK may be involved in the above process. Then, apoptotic signal is amplified by activation of caspase and leads to cell death.


Sialic acid-binding lectin (leczyme) induces caspase-dependent apoptosis-mediated mitochondrial perturbation in Jurkat cells.

Tatsuta T, Hosono M, Sugawara S, Kariya Y, Ogawa Y, Hakomori S, Nitta K - Int. J. Oncol. (2013)

Proposed model for apoptotic mechanism induced by SBL in Jurkat cells. SBL binds to cell surface and internalizes into tumor cells. SBL degrades cellular RNA and this ribotoxic stress triggers mitochondrial perturbation. Then, apoptotic signal is amplified by caspase activation leading to cell death.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3823373&req=5

f8-ijo-43-05-1402: Proposed model for apoptotic mechanism induced by SBL in Jurkat cells. SBL binds to cell surface and internalizes into tumor cells. SBL degrades cellular RNA and this ribotoxic stress triggers mitochondrial perturbation. Then, apoptotic signal is amplified by caspase activation leading to cell death.
Mentions: SBL is a multifunctional protein which has lectin activity, ribonuclease activity and antitumor activity. The proposed mechanism of SBL-induced cell death is shown in Fig. 8. SBL binds to cell surface, internalizes into tumor cells and degrades cellular RNA and this ribotoxic stress triggers mitochondrial perturbation. The activation of p38 and JNK may be involved in the above process. Then, apoptotic signal is amplified by activation of caspase and leads to cell death.

Bottom Line: The precise mechanisms of SBL-induced apoptotic signals were analyzed by combinational usage of specific caspase inhibitors and the mitochondrial membrane depolarization detector JC-1.It was demonstrated that SBL causes mitochondrial perturbation and the apoptotic signal is amplified by caspases and cell death is executed in a caspase-dependent manner.The efficacy of this combinational usage was shown for the first time, to distinguish the apoptotic pathway in detail.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan.

ABSTRACT
Sialic acid binding lectin (SBL) isolated from Rana catesbeiana oocytes is a multifunctional protein which has lectin activity, ribonuclease activity and antitumor activity. However, the mechanism of antitumor effects of SBL is unclear to date and the validity for human leukemia cells has not been fully studied. We report here that SBL shows cytotoxicity for some human leukemia cell lines including multidrug-resistant (MDR) cells. The precise mechanisms of SBL-induced apoptotic signals were analyzed by combinational usage of specific caspase inhibitors and the mitochondrial membrane depolarization detector JC-1. It was demonstrated that SBL causes mitochondrial perturbation and the apoptotic signal is amplified by caspases and cell death is executed in a caspase-dependent manner. The efficacy of this combinational usage was shown for the first time, to distinguish the apoptotic pathway in detail. SBL selectively kills tumor cells, is able to exhibit cytotoxicity regardless of P-glycoprotein expression and has potential as an alternative to conventional DNA-damaging anticancer drugs.

Show MeSH
Related in: MedlinePlus