Cell death induction by Streptococcus pyogenes in four types of malignant cell lines (original) (raw)
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Bacteria in cancer therapy: a novel experimental strategy
Journal of Biomedical Science, 2010
Resistance to conventional anticancer therapies in patients with advanced solid tumors has prompted the need of alternative cancer therapies. Moreover, the success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity to normal tissues. Several decades after Coley's work a variety of natural and genetically modified non-pathogenic bacterial species are being explored as potential antitumor agents, either to provide direct tumoricidal effects or to deliver tumoricidal molecules. Live, attenuated or genetically modified non-pathogenic bacterial species are capable of multiplying selectively in tumors and inhibiting their growth. Due to their selectivity for tumor tissues, these bacteria and their spores also serve as ideal vectors for delivering therapeutic proteins to tumors. Bacterial toxins too have emerged as promising cancer treatment strategy. The most potential and promising strategy is bacteria based gene-directed enzyme prodrug therapy. Although it has shown successful results in vivo yet further investigation about the targeting mechanisms of the bacteria are required to make it a complete therapeutic approach in cancer treatment.
Bacterial Therapy of Cancer: Promises, Limitations, and Insights for Future Directions
Frontiers in Microbiology
Spontaneous tumors regression has been associated with microbial infection for 100s of years and inspired the use of bacteria for anticancer therapy. Dr. William B. Coley (1862-1936), a bone-sarcoma surgeon, was a pioneer in treating his patients with both live bacterial-based and mixture of heat-killed bacteria known as "Coley's toxins." Unfortunately, Coley was forced to stop his work which interrupted this field for about half a century. Currently, several species of bacteria are being developed against cancer. The bacterial species, their genetic background and their infectious behavior within the tumor microenvironment are thought to be relevant factors in determining their anti-tumor effectiveness in vivo. In this perspective article we will update the most promising results achieved using bacterial therapy (alone or combined with other strategies) in clinically-relevant animal models of cancer and critically discuss the impact of the bacterial variants, route of administration and mechanisms of bacteria-cancercell interaction. We will also discuss strategies to apply this information using modern mouse models, molecular biology, genetics and imaging for future bacterial therapy of cancer patients.
The role of bacteria in cancer therapy – enemies in the past, but allies at present
Infectious Agents and Cancer
In recent decades, bacteria's therapeutic role has aroused attention in medicinal and pharmaceutical research. While bacteria are considered among the primary agents for causing cancer, recent research has shown intriguing results suggesting that bacteria can be effective agents for cancer treatmentthey are the perfect vessels for targeted cancer therapy. Several bacterial strains/species have been discovered to possess inherent oncolytic potentials to invade and colonize solid tumors in vivo. The therapeutic strategy of using bacteria for treating cancer is considered to be effective; however, the severe side effects encountered during the treatment resulted in the abandonment of the therapy. State-of-the-art genetic engineering has been recently applied to bacteria therapy and resulted in a greater efficacy with minimum side effects. In addition, the anti-cancer potential of tumor-targeting bacteria through oral administration circumvents the use of the intravenous route and the associated adverse effects. This review aims to provide a comprehensive summary of the latest literature on the role of bacteria in cancer treatment.
The role of bacteria in the treatment of cancer: A comprehensive review
Plant Biotechnology Persa, 2020
Cancer is an important public health issue worldwide and is the main cause of death in the developed countries and the second cause of death in the developing countries. There are several treatments for cancer such as photodynamic therapy, surgery, chemotherapy, hormonal therapy, radiotherapy and immunotherapy. Current cancer treatments have various side effects, including the gradual resistance of cancer cells to treatment. The era of targeted cancer therapy has brought about new clinical approaches such as antibodies, small molecules, antiangiogenics, and antivirals. Yet even these strategies remain limited in their ability to accumulate in tumors and tumor penetration, which are the main obstacles in the treatment of cancer. Historic efforts to harness living organisms to fight cancer have recently been revived in the field of synthetic biology. Certain circulating bacteria can intrinsically home in on tumors, and can be engineered to controllably induce local cytotoxicity while remaining unobtrusive to the host system. Due to the ineffectiveness of conventional treatments such as chemotherapy and radiation therapy in advanced tumor stages, resistance to treatment and non-specificity of these treatments, with the advancement of studies in this field, it is hoped that bacterial therapy will add a new dimension to cancer treatment.
Therapeutic bacteria to combat cancer; current advances, challenges, and opportunities
Cancer Medicine
Cancer remains one of the most common causes of death throughout the world. 1-3 In 2018, the new cases and deaths of cancer were reported 18.1 and 9.6 million, respectively. 4 By 2030, it is expected that there will be ~17 million deaths. 1 These statistics emphasize the urgency of finding novel and more effective treatments. The historical treatment options
Bacteria in cancer therapy: beyond immunostimulation
Journal of Cancer Metastasis and Treatment, 2018
Currently, conventional therapies in cancer are improving; chemotherapy, radiotherapy and surgery have increased survival significantly. New therapies have arisen with the same goal; immunotherapy has appeared as a promising option in the fight against cancer stimulating the immune system by inducing innate and adaptive responses. These responses include release of pro-inflammatory cytokines, making the immune system capable to eliminate or protect against multiple tumors. Nowadays, many of these therapies are being used in clinical settings, such as checkpoint inhibitors, monoclonal anti cytotoxic T-Lymphocyte associated protein 4 (CTL-4) and programmed death protein 1 (PD1), with inspiring results; however, they may decrease immunotolerance, limiting their use. At the same time, chemotherapy works by passive transport across the cell membrane, limiting its capacity to penetrate in tumor cells. For these reasons, bacteria employment represents one of the best candidates for cancer treatment. They can surpass these barriers with their selective colonization which also has an oncolytic effect by increasing proliferation and immunostimulation in the tumor environment. Attenuated strains, such as Mycobacterium bovis, Clostridium, Salmonella typhimirium and Listeria monocytogenes have been studied showing promising results in experimental models. However, their application in clinical trials has shown the need to maximize their therapeutic effect. Genetic engineering and synthetic biology are necessary to prove the scope that this novel approach has against cancer due to implications of cancer therapy and public health.
International journal of molecular medicine, 2011
Although group B Streptococcus (GBS) has been classically described as an exclusively extracellular pathogen, growing evidence suggests that it may be internalized by epithelial cells. However, the fates of intracellular GBS and of infected respiratory epithelial cells remain unclear. Little is known about the bacterial components involved in these processes. The present study investigated the bacterial internalization by A549 cells and the apoptosis/necrosis of the infected human epithelial cells. The morphological changes in A549 cells observed from 2 h post-infection with GBS included vacuolization and the formation of apoptotic bodies. Flow cytometry revealed that 81.2% of apoptotic A549 cells were infected with GBS serotype III 90356-liquor. Moreover, a double-staining assay using propidium iodide (PI)/Annexin V (AV) gave information about the numbers of viable (PI-/AV-) (18.27%) vs. early apoptotic (PI-/AV+) (73.83%) and late apoptotic cells (PI+/AV+) (7.37%) during infection ...
Bacterial targeted tumour therapy-dawn of a new era
Cancer Letters, 2008
Original observation of patients' spontaneous recovery from advanced tumours after an infection or a ''fever'' inspired extensive research. As a result, Coley's toxin for the therapy of sarcomas and live Bacillus Calmette-Guerin (BCG) for bladder cancer were born. In addition, three genera of anaerobic bacteria have been shown to specifically and preferentially target solid tumours and cause significant tumour lyses. Initial research had focused on determining the best tumour colonizing bacteria, and assessing the therapeutic efficacy of different strategies either as a single or combination treatment modalities. However, although clinical trials were carried out as early as the 1960s, lack of complete tumour lyses with injection of Clostridial spores had limited their further use. Recent progress in the field has highlighted the rapid development of new tools for genetic manipulation of Clostridia which have otherwise been a hurdle for a long time, such as plasmid transformation using electroporation that bore the problems of inefficiency, instability and plasmid loss. A new Clostridium strain, C. novyi-NT made apathogenic by genetic modification, is under clinical trials. New genetic engineering tools, such as the group II intron has shown promise for genetic manipulation of bacteria and forecast the dawn of a new era for a tumour-targeted bacterial vector system for gene therapy of solid tumours. In this review we will discuss the potential of genetically manipulated bacteria that will usher in the new era of bacterial therapy for solid tumours, and highlight strategies and tools used to improve the bacterial oncolytic capability.
Antimicrobial Agents and Chemotherapy, 2011
Lactobacilli are known to prevent colonization by many pathogens; nevertheless, the mechanisms of their protective effect are largely unknown. In this work, we investigated the role of lactobacilli during infection of epithelial cells with group A streptococci (GAS). GAS cause a variety of illnesses ranging from noninvasive disease to more severe invasive infections, such as necrotizing fasciitis and toxic shock-like syndrome. Invasion of deeper tissues is facilitated by GAS-induced apoptosis and cell death. We found that lactobacilli inhibit GAS-induced host cell cytotoxicity and shedding of the complement regulator CD46. Further, survival assays demonstrated that lactic acid secreted by lactobacilli is highly bactericidal toward GAS. In addition, lactic acid treatment of GAS, but not heat killing, prior to infection abolishes the cytotoxic effects against human cells. Since lipoteichoic acid (LTA) of GAS is heat resistant and cytotoxic, we explored the effects of lactic acid on LTA. By applying such an approach, we demonstrate that lactic acid reduces epithelial cell damage caused by GAS by degrading both secreted and cell-bound LTA. Taken together, our experiments reveal a mechanism by which lactobacilli prevent pathogen-induced host cell damage.