Abstract
Currently, global efforts are being intensified towards the discovery of local Bacillus thuringiensis (Bt) isolates with unique anticancer properties. Parasporins (PS) are a group of Bt non-insecticidal crystal proteins with potential and specific in vitro anticancer activity. However, despite the significant therapeutic potential of PS-producing Bt strains, our current knowledge on the effects of these proteins is limited. Hence, the main objective of this study was to screen Bt-derived parasporal toxins for cytotoxic activities against colon (HT-29) and cervical (HeLa) cancerous cell lines. Nine non-larvicidal and non-hemolytic Bt strains, native to Saudi Arabia, were employed for the isolation of their parasporal toxins. 16S rDNA sequencing revealed a 99.5% similarity with a reference Bt strain. While PCR screening results indicated the absence of selected Cry (Cry4A, Cry4B, Cry10 and Cry11), Cyt (Cyt1 and Cyt2) and PS (PS2, PS3 and PS4) genes, it concluded presence of the PS1 gene. SDS-PAGE analysis revealed that proteolytically-cleavaged PS protein profiles exhibit patterns resembling those observed with PS1Aa1, with major bands at 56 kDa and 17 kDa (Bt7), and 41 kDa and 16 kDa (Bt5). Solubilized and trypsinized PS proteins from all Bt strains exhibited a marked and dose-dependent cytotoxicity against HeLa cancerous cells but not against HT-29 cells. IC50 values ranged from 3.2 (Bt1) to 14.2 (Bt6) with an average of 6.8 µg/mL. The observed cytotoxicity of PS proteins against HeLa cells was specific as it was not evident against normal uterus smooth muscle cells. RT-qPCR analysis revealed the overexpression of caspase 3 and caspase 9 by 3.7, and 4.2 folds, respectively, indicative of the engagement of intrinsic pathway of apoptosis. To the best of our knowledge, this is the first report exploring and exploiting the versatile repertoire of Saudi Arabian environmental niches for the isolation of native and possibly novel Saudi Bt strains with unique and specific anticancer activity. In conclusion, native Saudi Bt-derived PS proteins might have a potential to join the arsenal of natural anticancer drugs.
Highlights
Cancer is one of the leading causes of death worldwide and it poses a major global public health concern
Phase contrast microscopy revealed that all Bacillus thuringiensis (Bt) strains shared many morphological characteristics in cell chains arrangement, ellipsoidal shape of spores, and sporangia, in agreement with our previously published data [27]
Several experimental cancer treatments have been presented as medical therapies intended to treat cancer by improving, supplementing or replacing conventional methods
Summary
Cancer is one of the leading causes of death worldwide and it poses a major global public health concern. In 2018, a striking rise in global cancer burden has been reported with 18.1 million newly diagnosed cases, 9.6 million mortalities and 43.8 million people 5-year survival rate compared to only 12.4, 7.6 and 28 million people in 2008, respectively. In 2030, it is projected that these figures will continue to rise to an alarming 26.4 million newly diagnosed cases and 17 million cancer-related deaths [1]. Lung, breast and colorectal cancers account for one third of cancer incidence and mortality burden, are classified in the top three highly prevalent cancer types, and ranked within the top five in terms of death rates (1st, 5th and 2nd, respectively). Cervical cancer leads the race for both incidence (6.6%) and mortality (7.5%) being ranked fourth for both in women [1].
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