Enhancing an Oxidative “Trojan Horse” Action of Vitamin C with Arsenic Trioxide for Effective Suppression of KRAS-Mutant Cancers: A Promising Path at the Bedside
The turn-on mutations of the <i>KRAS</i> gene, coding a small GTPase coupling growth factor signaling, are contributing to nearly 25% of all human cancers, leading to highly malignant tumors with poor outcomes. Targeting of oncogenic KRAS remains a most challenging task in oncology. Rece...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/21/3454 |
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| author | Agata N. Burska Bayansulu Ilyassova Aruzhan Dildabek Medina Khamijan Dinara Begimbetova Ferdinand Molnár Dos D. Sarbassov |
| author_facet | Agata N. Burska Bayansulu Ilyassova Aruzhan Dildabek Medina Khamijan Dinara Begimbetova Ferdinand Molnár Dos D. Sarbassov |
| author_sort | Agata N. Burska |
| collection | DOAJ |
| description | The turn-on mutations of the <i>KRAS</i> gene, coding a small GTPase coupling growth factor signaling, are contributing to nearly 25% of all human cancers, leading to highly malignant tumors with poor outcomes. Targeting of oncogenic KRAS remains a most challenging task in oncology. Recently, the specific G12C mutant KRAS inhibitors have been developed but with a limited clinical outcome because they acquire drug resistance. Alternatively, exploiting a metabolic breach of KRAS-mutant cancer cells related to a glucose-dependent sensitivity to oxidative stress is becoming a promising indirect cancer targeting approach. Here, we discuss the use of a vitamin C (VC) acting in high dose as an oxidative “Trojan horse” agent for KRAS-mutant cancer cells that can be potentiated with another oxidizing drug arsenic trioxide (ATO) to obtain a potent and selective cytotoxic impact. Moreover, we outline the advantages of VC’s non-natural enantiomer, <i>D</i>-VC, because of its distinctive pharmacokinetics and lower toxicity. Thus, the <i>D</i>-VC and ATO combination shows a promising path to treat KRAS-mutant cancers in clinical settings. |
| first_indexed | 2024-03-09T19:11:20Z |
| format | Article |
| id | doaj.art-63c40894e1334db2ad76639131414761 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T19:11:20Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-63c40894e1334db2ad766391314147612023-11-24T04:09:01ZengMDPI AGCells2073-44092022-11-011121345410.3390/cells11213454Enhancing an Oxidative “Trojan Horse” Action of Vitamin C with Arsenic Trioxide for Effective Suppression of KRAS-Mutant Cancers: A Promising Path at the BedsideAgata N. Burska0Bayansulu Ilyassova1Aruzhan Dildabek2Medina Khamijan3Dinara Begimbetova4Ferdinand Molnár5Dos D. Sarbassov6Department of Biology, Nazarbayev University, Astana 010000, KazakhstanDepartment of Biology, Nazarbayev University, Astana 010000, KazakhstanDepartment of Biology, Nazarbayev University, Astana 010000, KazakhstanDepartment of Biology, Nazarbayev University, Astana 010000, KazakhstanNational Laboratory Astana, Nazarbayev University, Astana 010000, KazakhstanDepartment of Biology, Nazarbayev University, Astana 010000, KazakhstanDepartment of Biology, Nazarbayev University, Astana 010000, KazakhstanThe turn-on mutations of the <i>KRAS</i> gene, coding a small GTPase coupling growth factor signaling, are contributing to nearly 25% of all human cancers, leading to highly malignant tumors with poor outcomes. Targeting of oncogenic KRAS remains a most challenging task in oncology. Recently, the specific G12C mutant KRAS inhibitors have been developed but with a limited clinical outcome because they acquire drug resistance. Alternatively, exploiting a metabolic breach of KRAS-mutant cancer cells related to a glucose-dependent sensitivity to oxidative stress is becoming a promising indirect cancer targeting approach. Here, we discuss the use of a vitamin C (VC) acting in high dose as an oxidative “Trojan horse” agent for KRAS-mutant cancer cells that can be potentiated with another oxidizing drug arsenic trioxide (ATO) to obtain a potent and selective cytotoxic impact. Moreover, we outline the advantages of VC’s non-natural enantiomer, <i>D</i>-VC, because of its distinctive pharmacokinetics and lower toxicity. Thus, the <i>D</i>-VC and ATO combination shows a promising path to treat KRAS-mutant cancers in clinical settings.https://www.mdpi.com/2073-4409/11/21/3454Kirsten rat sarcoma (KRAS) mutant ancersWarburg effectoxidative stressarsenic trioxide (ATO)vitamin C (VC also known as ascorbic acid)reactive oxygen species (ROS) |
| spellingShingle | Agata N. Burska Bayansulu Ilyassova Aruzhan Dildabek Medina Khamijan Dinara Begimbetova Ferdinand Molnár Dos D. Sarbassov Enhancing an Oxidative “Trojan Horse” Action of Vitamin C with Arsenic Trioxide for Effective Suppression of KRAS-Mutant Cancers: A Promising Path at the Bedside Cells Kirsten rat sarcoma (KRAS) mutant ancers Warburg effect oxidative stress arsenic trioxide (ATO) vitamin C (VC also known as ascorbic acid) reactive oxygen species (ROS) |
| title | Enhancing an Oxidative “Trojan Horse” Action of Vitamin C with Arsenic Trioxide for Effective Suppression of KRAS-Mutant Cancers: A Promising Path at the Bedside |
| title_full | Enhancing an Oxidative “Trojan Horse” Action of Vitamin C with Arsenic Trioxide for Effective Suppression of KRAS-Mutant Cancers: A Promising Path at the Bedside |
| title_fullStr | Enhancing an Oxidative “Trojan Horse” Action of Vitamin C with Arsenic Trioxide for Effective Suppression of KRAS-Mutant Cancers: A Promising Path at the Bedside |
| title_full_unstemmed | Enhancing an Oxidative “Trojan Horse” Action of Vitamin C with Arsenic Trioxide for Effective Suppression of KRAS-Mutant Cancers: A Promising Path at the Bedside |
| title_short | Enhancing an Oxidative “Trojan Horse” Action of Vitamin C with Arsenic Trioxide for Effective Suppression of KRAS-Mutant Cancers: A Promising Path at the Bedside |
| title_sort | enhancing an oxidative trojan horse action of vitamin c with arsenic trioxide for effective suppression of kras mutant cancers a promising path at the bedside |
| topic | Kirsten rat sarcoma (KRAS) mutant ancers Warburg effect oxidative stress arsenic trioxide (ATO) vitamin C (VC also known as ascorbic acid) reactive oxygen species (ROS) |
| url | https://www.mdpi.com/2073-4409/11/21/3454 |
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