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A parasporin from Bacillus thuringiensis native to Peninsular India induces apoptosis in cancer cells through intrinsic pathway

Published on Jun 1, 2018in Journal of Biosciences1.823
· DOI :10.1007/s12038-018-9759-0
Thomas Chubicka2
Estimated H-index: 2
,
Devaki Girija1
Estimated H-index: 1
(College of Horticulture)
+ 5 AuthorsThekkekara Devassy Babu4
Estimated H-index: 4
Abstract
Parasporins, a class of non-insecticidal crystal proteins of Bacillus thuringiensis (Bt) are being explored as promising anticancer agents due to their specific toxicity to cancer cells. The present study has identified 25 Bt isolates harbouring parasporin genes from Western Ghats region, the hotspot of biodiversity in India. Among these, the isolate, KAU 41 (Kerala Agricultural University isolate 41) contained non-hemolytic homogenous crystals showing specific cytotoxicity towards cancer cells. SDS-PAGE analysis of this crystal, isolated by aqueous biphasic separation, revealed a 31 kDa sized peptide. The N-terminal sequence deciphered in BLAST analysis showed homology to a hypothetical Bt protein. Upon proteolysis, a 29 kDa active peptide was generated which exhibited heterogenic cytotoxic spectrum on various cancer cells. HeLa cells were highly susceptible to this peptide with IC50 1 µg/mL and showed characteristics of apoptosis. RT-qPCR analysis revealed the overexpression of APAF1, caspase 3 and 9 by 14.9, 8 and 7.4 fold, respectively which indicates the activation of intrinsic pathway of apoptosis. However, at higher concentrations of peptide (>3 µg/mL), necrotic death was prominent. The results suggest that the 31 kDa protein from Bt isolate, KAU 41 is a parasporin that may have high therapeutic potential.
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  • Citations (1)
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References32
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#1Leopoldo PalmaH-Index: 10
#2Delia MuñozH-Index: 19
Last. Primitivo CaballeroH-Index: 28
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Bacillus thuringiensis (Bt) is a Gram positive, spore-forming bacterium that synthesizes parasporal crystalline inclusions containing Cry and Cyt proteins, some of which are toxic against a wide range of insect orders, nematodes and human-cancer cells. These toxins have been successfully used as bioinsecticides against caterpillars, beetles, and flies, including mosquitoes and blackflies. Bt also synthesizes insecticidal proteins during the vegetative growth phase, which are subsequently secrete...
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#1N. K. Lenina (TNAU: Tamil Nadu Agricultural University)H-Index: 1
#2A. Naveenkumar (TNAU: Tamil Nadu Agricultural University)H-Index: 2
Last. V. Udayasuriyan (TNAU: Tamil Nadu Agricultural University)H-Index: 5
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Bacillus thuringiensis (Bt) is popularly known as insecticidal bacterium. However, non-insecticidal Bt strains are more extensively available in natural environment than the insecticidal ones. Parasporin (PS) is a collection of genealogically heterogeneous Cry proteins synthesized in non-insecticidal isolates of Bt. An important character generally related with PS proteins is their strong cytocidal activity preferentially on human cancer cells of various origins. Identification and characterizat...
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#1Shiro OkumuraH-Index: 10
#2Hiroyuki SaitohH-Index: 17
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Abstract Parasporin-4 (PS4) is a cytotoxic protein produced by Bacillus thuringiensis strain A1470. It exhibits specific cytotoxicity against human cancer cell lines, CACO-2, Sawano, and MOLT-4 cells, in particular. When cells were administrated with PS4, cell swelling and nuclear shrinkage were induced, and, the ballooned cells burst within 24 h. PSI-BLAST search showed that the protein shared homology not only with B. thuringiensis Cry toxins but also with aerolysin-type β-pore-forming toxins....
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#1A. Ramalakshmi (TNAU: Tamil Nadu Agricultural University)H-Index: 1
#2V. Udayasuriyan (TNAU: Tamil Nadu Agricultural University)H-Index: 1
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Bacillus thuringiensis (Bt) is a unique bacterium in that it shares a common place with a number of chemical compounds which are used commercially to control insects important to agriculture and public health. Although other bacteria, including B. popilliae and B. sphaericus, are used as microbial insecticides, their spectrum of insecticidal activity is quite limited compared to Bt. Importantly, Bt is safe for humans and is the most widely used environmentally compatible biopesticide worldwide. ...
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Parasporin (PS) is a collection of genealogically heterogeneous Cry proteins synthesized in Bacillus thuringiensis. A prominent feature commonly associated with PS proteins is the strong cytocidal activity preferential for human cancer cells of various origins. The proteins exhibit cytocidal activities only when digested with proteases. Currently, this protein group is classified into four families: PS1, PS2, PS3 and PS4. Marked differences are evident in cytotoxicity spectra and activity levels...
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A novel crystal protein that exhibited potent cytotoxicity against human leukemic T-cells was cloned from the Bacillus thuringiensis TK-E6 strain. The protein, designated as parasporin-2Ab (PS2Ab), was a polypeptide of 304 amino acid residues with a predicted molecular weight of 33,017. The deduced amino acid sequence of PS2Ab showed significant homology (84% identitiy) to parasporin-2Aa (PS2Aa) from the B. thuringiensis A1547 strain. Upon processing of PS2Ab with proteinase K, the active form o...
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Abstract Parasporin-1 is a novel non-insecticidal inclusion protein from Bacillus thuringiensis that is cytotoxic to specific mammalian cells. In this study, we investigated the effects of parasporin-1 on toxin-sensitive cell lines to elucidate the cytotoxic mechanism of parasporin-1. Parasporin-1 is not a membrane pore-forming toxin as evidenced by measurements of lactate dehydrogenase release, propidium iodide penetration, and membrane potential in parasporin-1-treated cells. Parasporin-1 decr...
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Parasporins (PS), a class of non-insecticidal and non-hemolytic crystal proteins of Bacillus thuringiensis (Bt), are being explored as promising anti-cancer agents due to their specific toxicity to cancer cells. This work is considered as a first initiative aiming at investigating Algerian soil Bt isolates’ activity and cytotoxic potential against cancer cells. A total of 48 Bacillus spp. were isolated from different sites in Algeria. Phenotypic and biochemical tests, 16S rDNA molecular identifi...
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