Identification of a cytotoxic factor from a non-pigmented entomopathogenic Serratia marcescens isolate toxic towards human carcinoma cell lines
Related Experiment Video
Updated: Aug 8, 2025
Functional Characterization of Carboxylesterases in Insecticide Resistant House Flies, Musca Domestica
Published on: August 23, 2018
Mónica L Pineda-Castellanos1, Jesús Santa-Olalla-Tapia2, María de C Gutiérrez3
1Laboratorio de Patogenicidad Molecular, Centro de Investigación en Dinámica Celular, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, 62209, Cuernavaca, Morelos, México.
Abstract:
It has been reported that cell-free culture broths and some proteins from pigmented and non-pigmented Serratia spp. are cytotoxic towards cancerous and non-cancerous human cell lines. Looking for new molecules toxic against human cancerous cells but harmless towards normal human cells, the aim of this work was (a) to determine whether cell-free broths from the entomopathogenic non-pigmented S. marcescens 81 (Sm81), S. marcescens 89 (Sm89) and S. entomophila (SeMor4.1) presented cytotoxic activity towards human carcinoma cell lines; (b) to identify and purify the associated cytotoxic factor(s) and (c) to evaluate whether the cytotoxic factor(s) was cytotoxic towards non-cancerous human cells. This research was focussed on the observed morphology changes and the proportion of remaining viable cells after incubation in the presence of cell-free culture broths from the Serratia spp isolates to evaluate cytotoxic activity. The results showed that broths from both S. marcescens isolates presented cytotoxic activity and induced cytopathic-like effects on the human neuroblastoma CHP-212 and the breast cancer MDA-MB-231 cells. Slight cytotoxicity was observed in the SeMor4.1 broth. A serralysin-like protein of 50 kDa was identified in Sm81 broth as responsible for cytotoxic activity after purification by ammonium sulphate precipitation and ion-exchange chromatography followed by tandem-mass spectrometry (LC-MS/MS). The serralysin-like protein was toxic against CHP-212 (neuroblastoma), SiHa (human cervical carcinoma) and D-54 (human glioblastoma) cell lines in a dose-dependent manner and showed no cytotoxic activity in primary cultures of normal non-cancerous human keratinocytes and fibroblasts. Therefore, this protein should be evaluated for a potential use as an anticancer agent.
Insights
Researchers identified a novel serralysin-like protein from Serratia marcescens that selectively targets cancer cells. This entomopathogenic bacterium-derived protein shows potent anticancer activity against neuroblastoma and glioblastoma, sparing normal human cells.
Area of Science:
- Microbiology
- Biochemistry
- Cancer Research
Background:
- Cell-free broths and proteins from Serratia spp. exhibit cytotoxicity against human cell lines.
- There is a need for novel therapeutic agents selectively toxic to cancer cells while sparing normal cells.
Purpose of the Study:
- To assess the cytotoxic potential of cell-free broths from entomopathogenic Serratia spp. against human carcinoma cell lines.
- To identify and purify cytotoxic factors from these broths.
- To evaluate the selectivity of these factors towards cancerous versus non-cancerous human cells.
Main Methods:
- Incubation of human carcinoma cell lines with cell-free culture broths.
- Morphological change analysis and viable cell proportion assessment.
- Purification of cytotoxic proteins using ammonium sulphate precipitation and ion-exchange chromatography.
- Identification of the protein via tandem mass spectrometry (LC-MS/MS).
Main Results:
- S. marcescens broths demonstrated significant cytotoxicity and induced cytopathic effects on neuroblastoma (CHP-212) and breast cancer (MDA-MB-231) cells.
- A 50 kDa serralysin-like protein was purified from S. marcescens broth and identified as the primary cytotoxic agent.
- The purified protein exhibited dose-dependent toxicity against neuroblastoma, cervical carcinoma (SiHa), and glioblastoma (D-54) cells.
- No cytotoxic activity was observed against normal human keratinocytes and fibroblasts.
Conclusions:
- Cell-free broths from S. marcescens isolates possess cytotoxic properties against specific human cancer cell lines.
- A novel 50 kDa serralysin-like protein from S. marcescens is selectively toxic to various human cancer cells.
- This protein demonstrates potential as a targeted anticancer therapeutic agent, warranting further investigation.
