Microbial based therapy of cancer: A new twist to an age old practice

Abstract

The use of bacteria in the regression of tumors has long been known. Various approaches for using bacteria in cancer therapy include the use of bacteria as sensitizing agents for chemotherapy, as delivery agents for cancer drugs and as agents for gene therapy. The tumor regression stimulated by infecting microorganisms has been attributed to activation of the immune system of the host. However, recent studies indicate that when tumorharboring mice with defective immune systems are infected with certain microorganisms, the regression of the tumor is still observed, suggesting that there are other host factors contributing to the microbial associated regression of tumors. Since the use of live or attenuated bacteria for tumor regression has associated toxic effects, studies are in progress to identify a pure microbial metabolite or any component of the microbial cell that might have anti-cancer activity. It has now been demonstrated that a redox protein from Pseudomonas aeruginosa, a cupredoxin, can enter into human cancer cells and trigger the apoptotic cell death. In vivo, this cupredoxin can lead to the regression of tumor growth in immunodeficient mice harboring xenografted melanomas and breast cancer tumors without inducing significant toxic effects, suggesting that it has potential anti-cancer activity. This bacterial protein interacts with p53 and modulates mammalian cellular activity. Hence, it could potentially be used as an anti-cancer agent for solid tumors and has translational value in tumor-targeted or in combinational-biochemotherapy strategies for cancer treatments. Here, we focus on diverse approaches to cancer biotherapy, including bacteriolytic and bacterially-derived anti-cancer agents with an emphasis on their mechanism of action and therapeutic potential.

Homology versus analogy: possible evolutionary relationship of immunoglobulins, cupredoxins, and Cu,Zn‐superoxide dismutase

“…Dwulet and Putnam (1981) noted a similarity in the copper-binding motifs of SOD and ceruloplasmin, a cupredoxin, although they were unable to establish homology due to the lack of amino acid sequence identity. Cupredoxins constitute a diverse array of electron transfer proteins (Adman, 1991) although recent work suggests possible roles of some cupredoxins of pathogenic bacteria in suppressing tumors as well as parasitic and microbial infections (Yamada et al, 2002;Punj et al, 2003Punj et al, , 2004Yamada et al, 2004;Chaudhari et al, 2006;Fialho et al, 2007). We have previously suggested a possible common evolutionary origin for Igs and cupredoxins and provide further supportive evidence here.…”

Listeria monocytogenes Promotes Tumor Growth via Tumor Cell Toll-Like Receptor 2 Signaling

“…Chronic inflammation promotes neoplastic cell growth, may contribute to neovascularization (6), and is proposed as an initiating factor in f15% of human tumors (7). Nevertheless, the use of bacterial vaccines for immunotherapy of tumors is being reexamined because bacterial vaccines might efficiently activate a durable and robust antitumor response (8,9). In particular, Listeria monocytogenes (Lm), a Gram-positive facultative intracellular bacterium, is being developed as a cancer vaccine platform because it can induce a potent innate and adaptive response (10)(11)(12).…”

PA‐MSHA inhibits proliferation and induces apoptosis through the up‐regulation and activation of caspases in the human breast cancer cell lines

“…Anaerobic bacteria have been employed in treating cancer for a long time-almost 150 years [Samuilov, 2003;Punj et al, 2004b]. The use of live microorganisms has been validated for inhibiting tumor growth involving breast tumor cells [Samuilov, 2003], but it is always associated with infectious or other side effects related to the microorganisms [Dang et al, 2001;Chakrabarty, 2003].…”