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

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.

Malignant mesothelioma as an oxidative stress-induced cancer: An update

“…In their study, the combined use of SBL and TRAIL resulted in higher activation of caspase-8, which cleaved Bid and promoted its translocation into mitochondria. Bid, a proapoptotic member of the Bcl-2 family, perturbed mitochondrial function and led to cell apoptosis [124], supporting the findings of an earlier study showing the involvement of the same mechanism when cisplatin and soluble FAS ligand were used in combination to induce MM cell apoptosis [125]. In another study, α-tocopheryl succinate (α-TOS) was targeted to the mitochondria of MM cells and it was found to be more efficient in killing MM cells compared to the nontargeted α-TOS.…”

Drug resistance-related microRNAs in hematological malignancies: Translating basic evidence into therapeutic strategies

“…Cell apoptosis is a complex process that may be achieved through activation of a cascade of intracellular factors known as caspases [23][24][25]. Therefore, defects in these components involved in this process may cause uncontrolled cell proliferation, a crucial step in the development of MDR [26,27].…”

Antitumor Potential of Marine and Freshwater Lectins

“…In other words, as Aristotle would suggest, in medio stat virtus. When inside the cell, SBLc activates the intrinsic apoptotic pathway on more than 30 tumor cell lines representing leukemia [107][108][109]118,120,131,132], Burkitt's lymphoma [108,109], cervical [133], hepatocellular [120,121,133], and estrogen-positive and -negative breast carcinomas [113,114,116,117,120], glioblastoma [119], and malignant mesothelioma [110,113] (Table 3).…”