Dataset Information

Uncovering the Anticancer Potential of Murine Cytomegalovirus against Human Colon Cancer Cells.

ABSTRACT: Human cytomegalovirus (HCMV) components are often found in tumors, but the precise relationship between HCMV and cancer remains a matter of debate. Pro-tumor functions of HCMV were described in several studies, but an association between HCMV seropositivity and reduced cancer risk was also evidenced, presumably relying on recognition and killing of cancer cells by HCMV-induced lymphocytes. This study aimed at deciphering whether CMV influences cancer development in an immune-independent manner. Using immunodeficient mice, we showed that systemic infection with murine CMV (MCMV) inhibited the growth of murine carcinomas. Surprisingly, MCMV, but not HCMV, also reduced human colon carcinoma development in vivo. In vitro, both viruses infected human cancer cells. Expression of human interferon-? (IFN-?) and nuclear domain (ND10) were induced in MCMV-infected, but not in HCMV-infected human colon cancer cells. These results suggest a decreased capacity of MCMV to counteract intrinsic defenses in the human cellular host. Finally, immunodeficient mice receiving peri-tumoral MCMV therapy showed a reduction of human colon cancer cell growth, albeit no clinical sign of systemic virus dissemination was evidenced. Our study, which describes a selective advantage of MCMV over HCMV to control human colon cancer, could pave the way for the development of CMV-based therapies against cancer.

SUBMITTER: Massara L

PROVIDER: S-EPMC7052516 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Uncovering the Anticancer Potential of Murine Cytomegalovirus against Human Colon Cancer Cells.

Massara Layal L Khairallah Camille C Yared Nathalie N Pitard Vincent V Rousseau Benoit B Izotte Julien J Giese Alban A Dubus Pierre P Gauthereau Xavier X Déchanet-Merville Julie J Capone Myriam M

Molecular therapy oncolytics 20200129

Human cytomegalovirus (HCMV) components are often found in tumors, but the precise relationship between HCMV and cancer remains a matter of debate. Pro-tumor functions of HCMV were described in several studies, but an association between HCMV seropositivity and reduced cancer risk was also evidenced, presumably relying on recognition and killing of cancer cells by HCMV-induced lymphocytes. This study aimed at deciphering whether CMV influences cancer development in an immune-independent manner. ...[more]

PMID: 32140563

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Project description:UnlabelledBackgroundBenzimidazole derivatives are structurally bioisosteres of naturally occurring nucleotides, which makes them compatible with biopolymers of living systems. This property gives benzimidazole a biological and clinical importance. In the last decade, this class of compounds has been reported to possess anti-allergic, anti-diabatic, anti-HIV, anti-hypertensive, anti-inflammatory, anti-mycobacterial, anti-oxidant, anti-protozoal, and anti-viral properties. The researchers are now interested to explore their potential as anti-cancer agents. In the present study, an effort was made to further explore this area of research. Furthermore, in order to increase the solubility and efficacy of these heterocycles, the interest is now shifted to the salts of these compounds. With this background, we planned to synthesize a series of meta-xylyl linked bis-benzimidazolium salts to assess their anti-proliferation efficacy on human colon cancer cell line (HCT 116).ResultsA number of N-alkylbenzimidazoles were synthesized by reactions of benzimidazole with alkyl halides (i-PrBr, PrBr, EthBr, Pent-2-ylBr, BuBr, BenzCl, HeptBr). The subsequent treatment of the resulting N-alkylbenzimidazoles with 1,3-(bromomethylene)benzene afforded corresponding bis-benzimidazolium salts. All synthesized compounds were characterized by spectroscopic techniques (Additional file 1: NMR & FT-IR) and microanalysis. Molecular structures of selected compounds were established through single crystal x-ray diffraction studies. All the compounds were assessed for their anti-proliferation test on human colorectal cancer cell line (HCT 116). Results showed that the compounds exhibited dose dependent cytotoxicity towards the colon cancer cells with IC50 ranges between 0.1 to 17.6 ?M. The anti-proliferation activity of all compounds was more pronounced than that of standard reference drug 5-flourouracil (IC50 =19.2 ?M).ConclusionsAll the synthesized bis-benzimidazolium salts showed potential anticancer activity. Out of them, some of these salts showed IC50 value as low as 0.1-0.2 ?M. Based on the results it can be concluded that, the bis-benzimidazolium salts could probably be the potential source of chemotherapeutic drugs.

Dataset Information

Uncovering the Anticancer Potential of Murine Cytomegalovirus against Human Colon Cancer Cells.

Publications

Uncovering the Anticancer Potential of Murine Cytomegalovirus against Human Colon Cancer Cells.

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