BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation

Bezerra, Patrícia Heloise Alves; Ferreira, Isadora Marques; Franceschi, Beatriz Tinoco; Bianchini, F.; Ambrósio, Luciana; Cintra, Adélia Cristina Oliveira; Sampaio, Suely Vilela; Castro, Fabíola Attié de; Torqueti, Maria Regina

doi:10.1590/1678-9199-jvatitd-2019-0010

Cited by 24 publications

(15 citation statements)

References 33 publications

(39 reference statements)

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“…In this context, this study indicated that GNP-NN 32 was capable of inducing apoptosis at a concentration of 1.5 μg/mL in MCF-7 cell line and 5 μg/mL in MDA-MB-231 cell line. Our results are in agreement with other studies that discovered that disintegrin from Crotalus durissus collilineatus venom induced cytotoxicity [37] whereas BthTX-I from Bothrops jararacussu induced apoptosis [38] and also showed antitumor and antimetastatic effects [39] on human breast cancer cell lines.…”

Section: Discussionsupporting

confidence: 93%

Anticancer potential of nanogold conjugated toxin GNP-NN-32 from Naja naja venom

Attarde

Pandit

2020

J. Venom. Anim. Toxins incl. Trop. Dis

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Background: Cancer is the second most common fatal disease in the world, behind cardiovascular disorders in the first place. It accounts for around 0.3 million deaths per year in India due to the lack of proper diagnostic facilities, prevention and treatment. Current therapeutic methods do not provide adequate protection and affect normal cells along with cancerous ones. Thus, there is a need for some alternative therapeutic strategy, preferably from natural products, which have been traditionally used for treatment of various diseases in the country. Methods: In this study, we have conjugated purified NN-32 toxin from Naja naja venom with gold nanoparticles and its anticancer potential was evaluated against human breast cancer cell lines. UV-Vis spectroscopy, dynamic light scattering, transmission electron microscopy, atomic force microscopy and zeta potential analysis were the techniques used for characterization of GNP-NN-32. Results: GNP-NN-32 showed dose-and time-dependent cytotoxicity against breast cancer cell lines (MCF-7 and MDA-MB-231). NN-32 and GNP-NN-32 induced apoptosis in both breast cancer cell lines. The results of CFSE cell proliferation study revealed that NN-32 and GNP-NN-32 arrested cell division in both MCF-7 and MDA-MB-231 cell lines resulting in inhibition of proliferation of these cancer cells. Conclusion: GNP-NN-32 showed an anticancer potential against human breast cancer cell lines. Analysis of detailed chemical characterization along with its cytotoxic property might help to perceive a new dimension of the anti-cancer potential of GNP-NN-32 that will enhance its biomedical function in near future.

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Section: Discussionsupporting

confidence: 93%

Anticancer potential of nanogold conjugated toxin GNP-NN-32 from Naja naja venom

Attarde

Pandit

2020

J. Venom. Anim. Toxins incl. Trop. Dis

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“…Previously, the spontaneous apoptosis rate for SKBR3 cells cultured in RPMI 1640 medium over 24 h was 15 ± 6%. 8 Here, cells with DNA that migrated greater than 126 μm, the minimum migration distance of the DNA ladder, were classified as apoptotic. We observed an apoptosis rate of 0.6% (i.e., 8 cells exhibited fragmented DNA out of 1394 cells; n = 3 chips).…”

Section: Resultsmentioning

confidence: 99%

“… 7 Bulk proteoform measurements have been made with standard Western blots to investigate the apoptosis pathways after dosing with specific drugs/chemicals. 8 − 10 …”

Section: Introductionmentioning

confidence: 99%

Programmed Cell-Death Mechanism Analysis Using Same-Cell, Multimode DNA and Proteoform Electrophoresis

Martinez

Herr

2021

ACS Meas. Sci. Au

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Gaining insight into the timing of cell apoptosis events requires single-cell-resolution measurements of cell viability. We explore the supposition that mechanism-based scrutiny of programmed cell death would benefit from same-cell analysis of both the DNA state (intact vs fragmented) and the protein states, specifically the full-length vs cleaved state of the DNA-repair protein PARP1, which is cleaved by caspase-3 during caspase-dependent apoptosis. To make this same-cell, multimode measurement, we introduce the single-cell electrophoresis-based viability and protein (SEVAP) assay. Using SEVAP, we (1) isolate human breast cancer SKBR3 cells in microwells molded in thin polyacrylamide gels, (2) electrophoretically separate protein molecular states and DNA molecular states—using differences in electrophoretic mobility—from each single-cell lysate, and (3) perform in-gel DNA staining and PARP1 immunoprobing. Performed in an open microfluidic device, SEVAP scrutinized hundreds to thousands of individual SKBR3 cells. In each single-cell lysate separation, SEVAP baseline-resolved fragmented DNA from intact DNA ( R s = 5.17) as well as cleaved PARP1 from full-length PARP1 ( R s = 0.66). Comparing apoptotic and viable cells showed statistically similar profiles (expression, mobility, peak width) of housekeeping protein β-tubulin (Mann–Whitney U test). Clustering and cross-correlation analysis of DNA migration and PARP1 migration identified nonapoptotic vs apoptotic cells. Clustering analysis further suggested that cleaved PARP1 is a suitable apoptosis marker for this system. SEVAP is an efficient, multimode, end-point assay designed to elucidate cell-to-cell heterogeneity in mechanism-specific signaling during programmed cell death.

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“…Metalloproteases, serine proteases, LAAOs, and PLA2s are some of the most abundant proteins present in bothropic venoms, and the toxic action of these proteins are responsible for myotoxic effects, disruption in the coagulation cascade through thrombin-like proteins (serine proteases), imbalance in the blood homeostasis by the action of some metalloproteinases, apoptosis induction, and changes in the protein expression in oxidative stress and energy metabolism by the increase of Ca 2+ influx. Several studies have revealed that these enzymes are critical regulators of cancer pathologies in several types of cancers including breast cancer [ 121 , 122 , 123 , 124 , 125 , 126 , 127 ]. Moreover, it has been previously shown that B. jararaca venom may have an important antitumor effect on Ehrilich ascites tumor cells in vivo and in vitro [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines

Kisaki

Arcos

Montoni

et al. 2021

Toxins

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Cancer is characterized by the development of abnormal cells that divide in an uncontrolled way and may spread into other tissues where they may infiltrate and destroy normal body tissue. Several previous reports have described biochemical anti-tumorigenic properties of crude snake venom or its components, including their capability of inhibiting cell proliferation and promoting cell death. However, to the best of our knowledge, there is no work describing cancer cell proteomic changes following treatment with snake venoms. In this work we describe the quantitative changes in proteomics of MCF7 and MDA-MB-231 breast tumor cell lines following treatment with Bothrops jararaca snake venom, as well as the functional implications of the proteomic changes. Cell lines were treated with sub-toxic doses at either 0.63 μg/mL (low) or 2.5 μg/mL (high) of B. jararaca venom for 24 h, conditions that cause no cell death per se. Proteomics analysis was conducted on a nano-scale liquid chromatography coupled on-line with mass spectrometry (nLC-MS/MS). More than 1000 proteins were identified and evaluated from each cell line treated with either the low or high dose of the snake venom. Protein profiling upon venom treatment showed differential expression of several proteins related to cancer cell metabolism, immune response, and inflammation. Among the identified proteins we highlight histone H3, SNX3, HEL-S-156an, MTCH2, RPS, MCC2, IGF2BP1, and GSTM3. These data suggest that sub-toxic doses of B. jararaca venom have potential to modulate cancer-development related protein targets in cancer cells. This work illustrates a novel biochemical strategy to identify therapeutic targets against cancer cell growth and survival.

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BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation

Cited by 24 publications

References 33 publications

Anticancer potential of nanogold conjugated toxin GNP-NN-32 from Naja naja venom

Anticancer potential of nanogold conjugated toxin GNP-NN-32 from Naja naja venom

Programmed Cell-Death Mechanism Analysis Using Same-Cell, Multimode DNA and Proteoform Electrophoresis

Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines

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