Abstract
Traditional cancer treatments, such as chemotherapy and radiation therapy continue to have limited efficacy due to tumor hypoxia. While bacterial cancer therapy has the potential to overcome this problem, it comes with the risk of toxicity and infection. To circumvent these issues, this paper investigates the anti-tumor effects of non-viable bacterial derivatives of Clostridium sporogenes. These non-viable derivatives are heat-inactivated C. sporogenes bacteria (IB) and the secreted bacterial proteins in culture media, known as conditioned media (CM). In this project, the effects of IB and CM on CT26 and HCT116 colorectal cancer cells were examined on a 2-Dimensional (2D) and 3-Dimensional (3D) platform. IB significantly inhibited cell proliferation of CT26 to 6.3% of the control in 72 hours for the 2D monolayer culture. In the 3D spheroid culture, cell proliferation of HCT116 spheroids notably dropped to 26.2%. Similarly the CM also remarkably reduced the cell-proliferation of the CT26 cells to 2.4% and 20% in the 2D and 3D models, respectively. Interestingly the effect of boiled conditioned media (BCM) on the cells in the 3D model was less inhibitory than that of CM. Thus, the inhibitive effect of inactivated C. sporogenes and its conditioned media on colorectal cancer cells is established.
Highlights
Cells[7,8]
Wild-type clostridial spores have been found to exert oncolytic effects on tumors[22,23], clostridial spores combined with other cancer therapies were found to have an enhanced anti-cancer effect[24,25], and genetically modified clostridial species have been used in Clostridium-directed enzyme prodrug therapy (CDEPT)[16,20,21,26]
This paper studies the effect of heat-inactivated C. sporogenes bacteria (IB) on colorectal cancer cells for the first time, using CT26 and HCT116 cell lines
Summary
Cells[7,8]. Secondly, some drugs such as melphalan[9,10], bleomycin[11] and etoposide[12,13] require cellular oxygen to bring about cell death and are ineffective in hypoxic conditions. Clostridium perfringens enterotoxin (CPE) has been studied extensively and found to interact with claudin-3 and -4 receptors that are overexpressed in many types of tumors, to trigger cancer cell death[29,30] Despite these advances, clostridial cancer therapy has not gained widespread acceptance as a potential treatment method. Using anaerobic bacteria leaves a viable rim of tumor cells which increases the chance of tumor recurrence[22,35,36,37] Another point to note is that in vitro studies done in the field of bacterial cancer therapy are performed using 2-dimensional (2D) cancer cell cultures[38,39]. We hypothesize that the non-viable derivatives of C. sporogenes, IB and CM, can inhibit colorectal cancer cells
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