Safety profile of sikamat virus and its oncolytic potential in leukemic cells and cancer stem cells
Leukaemia remains a global health concern. The oncotherapy resistance of leukaemia might be due to the existence of cancer stem cell populations. This study investigated the therapeutic potential of Sikamat virus (PRV7S), a Pteropine orthoreovirus, as an oncolytic virus against acute myeloid leukaem...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Research
2025
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| Online Access: | http://psasir.upm.edu.my/id/eprint/120642/ http://psasir.upm.edu.my/id/eprint/120642/1/120642.pdf |
| _version_ | 1848868214091546624 |
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| author | Siew, Zhen Yun Ong, Ghee Khang Wong, Siew Tung Leong, Pooi Pooi Tan, Boon Shing Leong, Chee-Onn Chupri, Juita Fang, Chee-Mun Voon, Kenny |
| author_facet | Siew, Zhen Yun Ong, Ghee Khang Wong, Siew Tung Leong, Pooi Pooi Tan, Boon Shing Leong, Chee-Onn Chupri, Juita Fang, Chee-Mun Voon, Kenny |
| author_sort | Siew, Zhen Yun |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Leukaemia remains a global health concern. The oncotherapy resistance of leukaemia might be due to the existence of cancer stem cell populations. This study investigated the therapeutic potential of Sikamat virus (PRV7S), a Pteropine orthoreovirus, as an oncolytic virus against acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML). Using AML and CML cell lines (THP-1 and K562), as well as an AML-M5-derived cancer stem cell (CSC) model, PRV7S was shown to infect these leukaemic cells, replicate within them, and reduce their viability. PRV7S-induced cell death was associated with caspase-mediated apoptosis without significant cell cycle arrest. Transcriptomic and proteomic analyses revealed that PRV7S infection altered several cell death pathways, including apoptosis and necroptosis, highlighting its complex cell death mechanisms. PRV7S replicated efficiently in infected cells, though it did not cause persistent infection. An in vivo safety evaluation in immunocompetent mice demonstrated that PRV7S was well-tolerated, showing no adverse effects on survival, body weight, or histopathology, and no evidence of viral persistence. These findings suggest PRV7S as a promising oncolytic candidate for myeloid leukaemia, with potential efficacy against CSCs and a favourable safety profile. In conclusion, the study provides new insights into the cellular pathways involved in PRV7S-mediated oncolysis and supports further exploration of PRV7S’s potential against resistant leukaemic and solid tumours. |
| first_indexed | 2025-11-15T14:48:50Z |
| format | Article |
| id | upm-120642 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T14:48:50Z |
| publishDate | 2025 |
| publisher | Nature Research |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1206422025-10-07T04:21:45Z http://psasir.upm.edu.my/id/eprint/120642/ Safety profile of sikamat virus and its oncolytic potential in leukemic cells and cancer stem cells Siew, Zhen Yun Ong, Ghee Khang Wong, Siew Tung Leong, Pooi Pooi Tan, Boon Shing Leong, Chee-Onn Chupri, Juita Fang, Chee-Mun Voon, Kenny Leukaemia remains a global health concern. The oncotherapy resistance of leukaemia might be due to the existence of cancer stem cell populations. This study investigated the therapeutic potential of Sikamat virus (PRV7S), a Pteropine orthoreovirus, as an oncolytic virus against acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML). Using AML and CML cell lines (THP-1 and K562), as well as an AML-M5-derived cancer stem cell (CSC) model, PRV7S was shown to infect these leukaemic cells, replicate within them, and reduce their viability. PRV7S-induced cell death was associated with caspase-mediated apoptosis without significant cell cycle arrest. Transcriptomic and proteomic analyses revealed that PRV7S infection altered several cell death pathways, including apoptosis and necroptosis, highlighting its complex cell death mechanisms. PRV7S replicated efficiently in infected cells, though it did not cause persistent infection. An in vivo safety evaluation in immunocompetent mice demonstrated that PRV7S was well-tolerated, showing no adverse effects on survival, body weight, or histopathology, and no evidence of viral persistence. These findings suggest PRV7S as a promising oncolytic candidate for myeloid leukaemia, with potential efficacy against CSCs and a favourable safety profile. In conclusion, the study provides new insights into the cellular pathways involved in PRV7S-mediated oncolysis and supports further exploration of PRV7S’s potential against resistant leukaemic and solid tumours. Nature Research 2025-04-22 Article PeerReviewed text en cc_by_4 http://psasir.upm.edu.my/id/eprint/120642/1/120642.pdf Siew, Zhen Yun and Ong, Ghee Khang and Wong, Siew Tung and Leong, Pooi Pooi and Tan, Boon Shing and Leong, Chee-Onn and Chupri, Juita and Fang, Chee-Mun and Voon, Kenny (2025) Safety profile of sikamat virus and its oncolytic potential in leukemic cells and cancer stem cells. Scientific Reports, 15 (1). art. no. 13817. pp. 1-26. ISSN 2045-2322 https://www.nature.com/articles/s41598-025-96061-z?error=cookies_not_supported&code=0c10635b-4c6e-4193-93fb-fc40a9916c9b 10.1038/s41598-025-96061-z |
| spellingShingle | Siew, Zhen Yun Ong, Ghee Khang Wong, Siew Tung Leong, Pooi Pooi Tan, Boon Shing Leong, Chee-Onn Chupri, Juita Fang, Chee-Mun Voon, Kenny Safety profile of sikamat virus and its oncolytic potential in leukemic cells and cancer stem cells |
| title | Safety profile of sikamat virus and its oncolytic potential in leukemic cells and cancer stem cells |
| title_full | Safety profile of sikamat virus and its oncolytic potential in leukemic cells and cancer stem cells |
| title_fullStr | Safety profile of sikamat virus and its oncolytic potential in leukemic cells and cancer stem cells |
| title_full_unstemmed | Safety profile of sikamat virus and its oncolytic potential in leukemic cells and cancer stem cells |
| title_short | Safety profile of sikamat virus and its oncolytic potential in leukemic cells and cancer stem cells |
| title_sort | safety profile of sikamat virus and its oncolytic potential in leukemic cells and cancer stem cells |
| url | http://psasir.upm.edu.my/id/eprint/120642/ http://psasir.upm.edu.my/id/eprint/120642/ http://psasir.upm.edu.my/id/eprint/120642/ http://psasir.upm.edu.my/id/eprint/120642/1/120642.pdf |