Biotoxins for Cancer Therapy

Liu, Cuicui; Yang, Hao; Zhang, Lingling; Zhang, Qian; Chen, Bin; Wang, Yi

doi:10.7314/apjcp.2014.15.12.4753

Cited by 46 publications

(30 citation statements)

References 50 publications

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“…Therefore, new treatments for various types of cancers, including cervical cancer [9, 10], are considered one of the greatest challenges to medicine today because of the resistance to the effects due to repeated exposure [11]. Interventions with the use of chemotherapy are far from satisfactory, because of side effects, destruction of healthy cells, and above all acquired resistance by tumors [12–14]. …”

Section: Introductionmentioning

confidence: 99%

Bothrops jararaca and Bothrops erythromelas Snake 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

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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.

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Section: Introductionmentioning

confidence: 99%

Bothrops jararaca and Bothrops erythromelas Snake 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

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“…In order to overcome cDDP resistance and reduce normal cell toxicity, combination therapies of cDDP with other drugs, especially natural toxins have been highly considered. In the search for new cancer agents, biotoxins have recently attracted attention owing to their novel mode of actions and decreased possibility of resistance development (Gaspar et al 2013;Gajski et al 2014;Liu et al 2014). Bee venom (BV) has been used in oriental medicine as a source of drugs to cure different disorders (Son et al 2007;Oršolić 2012;Liu et al 2014;Premratanachai and Chanchao 2014).…”

Section: Introductionmentioning

confidence: 99%

Antitumour action on human glioblastoma A1235 cells through cooperation of bee venom and cisplatin

et al. 2015

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Cisplatin (cDDP) is one of the most widely used anticancer-drugs in both therapy and research. However, cDDP-resistance is the greatest obstacle for the successful treatment of cancer patients. In the present study, the possible joint anticancer effect of bee venom (BV), as a natural toxin, and cDDP towards human glioblastoma A1235 cells was evaluated. Treatment with BV alone in concentrations of 2.5-30 μg/ml displayed dose-dependent cytotoxicity towards A1235 cells, as evaluated with different cytotoxicity assays (MTT, Cristal violet and Trypan blue exclusion assay), with an IC50 value of 22.57 μg/ml based on the MTT results. Furthermore, BV treatment induced necrosis, which was confirmed by typical morphological features and fast staining with ethidium-bromide dye. Pre-treatment with BV induced cell sensitization to cDDP, indicating that BV could improve the killing effect of selected cells when combined with cDDP. The isobologram method used to determine the extent of synergism in combining two agents to examine their possible therapeutic effect showed that combined treatment induced an additive and/or synergistic effect towards selected cells depending on the concentration of both. Hence, a greater anticancer effect could be triggered if BV was used in the course of chemotherapy. The obtained results indicate that joint treatment with BV could be useful from the point of minimizing the cDDP concentration during chemotherapy, thus reducing and/or postponing the development of drug resistance. Our data, in accordance with previously reported results, suggests that BV could be used in the development of a new strategy for cancer treatment.

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“…Furthermore, Liu et al4 and Calderon et al34 reported many anticancer bioactive molecules present in the snake venoms. In our study, we also observed cell disintegrity that was clearly observable due to severe distortion in colony formation and cell movement in the snake-venom-treated cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…The abundance of this enzyme is responsible for neuro- and cytotoxicities, edema, thrombocytopenia, and impairment of blood clotting factors 3. In addition, researchers have discovered the presence of l -amino acid oxidase and disintegrin in snake venoms that can damage cellular integrity 4. Interestingly, under proper pharmacological regulation, snake venoms can be beneficial in treating certain types of chronic diseases including cancer.…”

Section: Introductionmentioning

confidence: 99%

Snake venom causes apoptosis by increasing the reactive oxygen species in colorectal and breast cancer cell lines

Alasmari

Riyasdeen

Al-Shahrani³

et al. 2016

OTT

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Snake venom possesses various kinds of proteins and neurotoxic polypeptides, which can negatively interfere with the neurotransmitter signaling cascade. This phenomenon occurs mainly due to the blocking of ion channels in the body system. Envenomation prevents or severely interrupts nerve impulses from being transmitted, inhibition of adenosine triphosphate synthesis, and proper functioning of the cardiac muscles. However, some beneficial properties of venoms have also been reported. The aim of this study was to examine the snake venom as an anticancer agent due to its inhibitory effects on cancer progression such as cell motility, cell invasion, and colony formation. In this study, the effect of venoms on phenotypic changes and the change on molecular level in colorectal and breast cancer cell lines were examined. A reduction of 60%–90% in cell motility, colony formation, and cell invasion was observed when these cell lines were treated with different concentrations of snake venom. In addition, the increase in oxidative stress that results in an increase in the number of apoptotic cancer cells was significantly higher in the venom-treated cell lines. Further analysis showed that there was a decrease in the expression of pro-inflammatory cytokines and signaling proteins, strongly suggesting a promising role for snake venom against breast and colorectal cancer cell progression. In conclusion, the snake venoms used in this study showed significant anticancer properties against colorectal and breast cancer cell lines.

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Biotoxins for Cancer Therapy

Cited by 46 publications

References 50 publications

Bothrops jararaca and Bothrops erythromelas Snake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells

Bothrops jararaca and Bothrops erythromelas Snake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells

Antitumour action on human glioblastoma A1235 cells through cooperation of bee venom and cisplatin

Snake venom causes apoptosis by increasing the reactive oxygen species in colorectal and breast cancer cell lines

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