Antitumor potential of the myotoxin BthTX-I from Bothrops jararacussu snake venom: evaluation of cell cycle alterations and death mechanisms induced in tumor cell lines

Silva, Cássio Prinholato da; Costa, Tássia R.; Paiva, Raquel Melo Alves; Cintra, Adélia Cristina Oliveira; Menaldo, Danilo L.; Antunes, Lusânia Maria Greggi; Sampaio, Suely Vilela

doi:10.1186/s40409-015-0044-5

Cited by 37 publications

(17 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To better understand the damage to the DNA of SiHa cell, the cell cycle was analyzed and it was found that BJ and BE were able to induce a change in the cell cycle promoting prevention at G0/G1 phase and not allowing the tumor cell to enter mitosis. The main findings of this article are similar to Prinholato da Silva et al's [32], who examined the cell cycle arrest in PC-12 (murine pheochromocytoma) and B16F10 (murine melanoma) tumors when treated with BthTX-I B. jararacussu .…”

Section: Discussionsupporting

confidence: 84%

“…What is more, Prinholato da Silva et al [32] demonstrated in different tumor cells HL-60 (promyelocytic leukemia), HepG2 (human hepatocellular carcinoma), PC-12 (murine pheochromocytoma), and B16F10 (murine melanoma) which BthTX-I toxin isolated from snake venom of B. jararacussu induced these cell deaths via apoptosis and/or necrosis in concentrations tested (25, 50, or 100 μ g/mL). While other studies have shown that snake venom toxins inhibited tumor growth accompanied with inactivation of nuclear factor kappa B (NF- κ B), thereby preventing human cervical cancer cell growth (CaSki and C33A) by the induction of apoptotic cell death [2].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Bothrops jararacaandBothrops erythromelasSnake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells

Bernardes-Oliveira

Gomes

Palomino

et al. 2016

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Bothrops jararaca (BJ) and Bothrops erythromelas (BE) are viper snakes found in South-Southeast and Northeast regions of Brazil, respectively. Snake venoms are bioactive neurotoxic substances synthesized and stored by venom glands, with different physiological and pharmacological effects, recently suggesting a possible preference for targets in cancer cells; however, mechanisms of snakes have been little studied. Here, we investigated the mechanism responsible for snake crude venoms toxicity in cultured cervical cancer cells SiHa and HeLa. We show that BJ and BE snake crude venoms exert cytotoxic effects to these cells. The percentage of apoptotic cells and cell cycle analysis and cell proliferation were assessed by flow cytometry and MTT assay. Detection of mitochondrial membrane potential (Rhodamine-123), nuclei morphological change, and DNA fragmentation were examined by staining with DAPI. The results showed that both the BJ and BE venoms were capable of inhibiting tumor cell proliferation, promoting cytotoxicity and death by apoptosis of target SiHa and HeLa cells when treated with BJ and BE venoms. Furthermore, data revealed that both BJ venoms in SiHa cell promoted nuclear condensation, fragmentation, and formation of apoptotic bodies by DAPI assay, mitochondrial damage by Rhodamine-123, and cell cycle block in the G1-G0 phase. BJ and BE venoms present anticancer potential, suggesting that both Bothrops venoms could be used as prototypes for the development of new therapies.

show abstract

Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Bothrops jararacaandBothrops erythromelasSnake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells

Bernardes-Oliveira

Gomes

Palomino

et al. 2016

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…This hypothesis will be tested in the future by checking HIF-1α expression in the control and treated group. Accumulated evidence shows that several isolated or recombinant snake venom toxins exhibit anti-cancer effects in vitro and in vivo preclinical models, triggering cell death via the mitochondrial intrinsic apoptotic pathway or necrosis [1,11,32]. Our results revealed that obtustatin did not induce any signs of apoptotic death in the treatment of animals with sarcoma.…”

Section: Discussionmentioning

confidence: 53%

The antitumor efficacy of monomeric disintegrin obtustatin in S-180 sarcoma mouse model

et al. 2019

View full text Add to dashboard Cite

Obtustatin, isolated from the Levantine Viper snake venom (Macrovipera lebetina obtusa-MLO), is the shortest known monomeric disintegrin shown to specifically inhibit the binding of the α1β1 integrin to collagen IV. Its oncostatic effect is due to the inhibition of angiogenesis, likely through α1β1 integrin inhibition in endothelial cells. To explore the therapeutic potential of obtustatin, we studied its effect in S-180 sarcoma-bearing mice model in vivo as well as in human dermal microvascular endothelial cells (HMVEC-D) in vitro, and tested anti-angiogenic activity in vivo using the chick embryo chorioallantoic membrane assay (CAM assay). Our in vivo results show that obtustatin inhibits tumour growth by 33%. The expression of vascular endothelial growth factor (VEGF) increased after treatment with obtustatin, but the level of expression of caspase 8 did not change. In addition, our results demonstrate that obtustatin inhibits FGF2-induced angiogenesis in the CAM assay. Our in vitro results show that obtustatin does not exhibit cytotoxic activity in HMVEC-D cells in comparison to in vivo results. Thus, our findings disclose that obtustatin might be a potential candidate for the treatment of sarcoma in vivo with low toxicity.

show abstract

“…There is also an increase in pro-apoptotic BAD expression and the activation of caspase 3 [56]. Moreover, PLA 2 alters the distribution of different phases in the cell cycle to cause apoptosis [57]. PLA 2 also exerts genotoxic effects to induce cytotoxicity in human lymphocytes [58].…”

Section: Mechanism Of Cytotoxicitymentioning

confidence: 99%

Cytotoxicity of snake venom enzymatic toxins: phospholipase A2 and l-amino acid oxidase

Hiu

Yap

2020

Biochemical Society Transactions

View full text Add to dashboard Cite

The phospholipase A 2 (PLA 2 ) and L-amino acid oxidase (LAAO) are two major enzymes found in the venoms from most snake species. These enzymes have been structurally and functionally characterised for their pharmacological activities. Both PLA 2 and LAAO from different venoms demonstrate considerable cytotoxic effects on cancer cells via induction of apoptosis, cell cycle arrest and suppression of proliferation. These enzymes produce more pronounced cytotoxic effects in cancer cells than normal cells, thus they can be potential sources as chemotherapeutic agents. It is proposed that PLA 2 and LAAO contribute to an elevated oxidative stress due to their catalytic actions, for instance, the ability of PLA 2 to produce reactive oxygen species during lipolysis and formation of H 2 O 2 from LAAO catalytic activity which consequently lead to cell death. Nonetheless, the cell-death signalling pathways associated with exposure to these enzymatic toxins are not fully elucidated yet. Here in this review, we will discuss the cytotoxic effects of PLA 2 and LAAO in relationship to their catalytic mechanisms and the underlying mechanisms of cytotoxic actions.

show abstract

Antitumor potential of the myotoxin BthTX-I from Bothrops jararacussu snake venom: evaluation of cell cycle alterations and death mechanisms induced in tumor cell lines

Cited by 37 publications

References 47 publications

Bothrops jararacaandBothrops erythromelasSnake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells

Bothrops jararacaandBothrops erythromelasSnake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells

The antitumor efficacy of monomeric disintegrin obtustatin in S-180 sarcoma mouse model

Cytotoxicity of snake venom enzymatic toxins: phospholipase A2 and l-amino acid oxidase

Contact Info

Product

Resources

About