Cannabichromene: integrative modulation of apoptosis, ferroptosis, and endocannabinoid signaling in pancreatic cancer therapy
Abstract Cannabichromene (CBC: C21H3O2, M.W.: 314.46 g) is a non-psychotropic phytocannabinoid derived from Cannabis sativa (hemp), and its potential therapeutic properties have attracted increasing attention. Specifically, it has demonstrated strong anti-inflammatory effects in animal models of ede...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-08-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02674-8 |
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| author | Yu-Na Hwang Ju-Hee Park Han-Heom Na Tae-Hyung Kwon Jin-Sung Park Sehyun Chae Young Taek Oh Keun-Cheol Kim |
| author_facet | Yu-Na Hwang Ju-Hee Park Han-Heom Na Tae-Hyung Kwon Jin-Sung Park Sehyun Chae Young Taek Oh Keun-Cheol Kim |
| author_sort | Yu-Na Hwang |
| collection | DOAJ |
| description | Abstract Cannabichromene (CBC: C21H3O2, M.W.: 314.46 g) is a non-psychotropic phytocannabinoid derived from Cannabis sativa (hemp), and its potential therapeutic properties have attracted increasing attention. Specifically, it has demonstrated strong anti-inflammatory effects in animal models of edema through non-CB receptor mechanisms; however, further pharmacological studies based on cancer models are required. In this study, we investigated the molecular mechanisms underlying the anti-cancer activity of CBC in human pancreatic cancer cells. Through mRNA-seq analysis, the expression levels of many genes involved in cell death pathways were upregulated or downregulated after CBC treatment, and these included ferroptosis-related genes, such as HMOX1. We further confirmed the functional validity of apoptosis and ferroptosis induction after CBC treatment using various molecular assays. In addition, CBC preferentially increased the expression of TRPV1 and CB2. Accordingly, the effects on cell death were reversed after treatment with TRPV1 and CB2 inhibitors, suggesting that receptor expression is necessary for the induction of apoptotic cell death. Finally, we confirmed the consistent regulation of apoptosis, ferroptosis, and endocannabinoid receptors during tumor growth inhibition after CBC treatment using in vivo xenograft models. Therefore, we propose that CBC exhibits pharmacological activity via the integrative modulation of multiple cell death pathways, which can be exploited for pancreatic cancer therapy. |
| format | Article |
| id | doaj-art-5662ce76514e42aeb4916d0b2eefdbd0 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-5662ce76514e42aeb4916d0b2eefdbd02025-08-20T03:42:26ZengNature Publishing GroupCell Death Discovery2058-77162025-08-0111111610.1038/s41420-025-02674-8Cannabichromene: integrative modulation of apoptosis, ferroptosis, and endocannabinoid signaling in pancreatic cancer therapyYu-Na Hwang0Ju-Hee Park1Han-Heom Na2Tae-Hyung Kwon3Jin-Sung Park4Sehyun Chae5Young Taek Oh6Keun-Cheol Kim7Department of Biological Sciences, College of Natural Sciences, Kangwon National UniversityDepartment of Biological Sciences, College of Natural Sciences, Kangwon National UniversityDepartment of Biological Sciences, College of Natural Sciences, Kangwon National UniversityChuncheon Bioindustry FoundationKorean Pharmacopuncture InstituteDivision of Chemical Engineering and Bioengineering, College of Art, Culture and Engineering, Kangwon National UniversityDepartment of Biological Sciences, College of Natural Sciences, Kangwon National UniversityDepartment of Biological Sciences, College of Natural Sciences, Kangwon National UniversityAbstract Cannabichromene (CBC: C21H3O2, M.W.: 314.46 g) is a non-psychotropic phytocannabinoid derived from Cannabis sativa (hemp), and its potential therapeutic properties have attracted increasing attention. Specifically, it has demonstrated strong anti-inflammatory effects in animal models of edema through non-CB receptor mechanisms; however, further pharmacological studies based on cancer models are required. In this study, we investigated the molecular mechanisms underlying the anti-cancer activity of CBC in human pancreatic cancer cells. Through mRNA-seq analysis, the expression levels of many genes involved in cell death pathways were upregulated or downregulated after CBC treatment, and these included ferroptosis-related genes, such as HMOX1. We further confirmed the functional validity of apoptosis and ferroptosis induction after CBC treatment using various molecular assays. In addition, CBC preferentially increased the expression of TRPV1 and CB2. Accordingly, the effects on cell death were reversed after treatment with TRPV1 and CB2 inhibitors, suggesting that receptor expression is necessary for the induction of apoptotic cell death. Finally, we confirmed the consistent regulation of apoptosis, ferroptosis, and endocannabinoid receptors during tumor growth inhibition after CBC treatment using in vivo xenograft models. Therefore, we propose that CBC exhibits pharmacological activity via the integrative modulation of multiple cell death pathways, which can be exploited for pancreatic cancer therapy.https://doi.org/10.1038/s41420-025-02674-8 |
| spellingShingle | Yu-Na Hwang Ju-Hee Park Han-Heom Na Tae-Hyung Kwon Jin-Sung Park Sehyun Chae Young Taek Oh Keun-Cheol Kim Cannabichromene: integrative modulation of apoptosis, ferroptosis, and endocannabinoid signaling in pancreatic cancer therapy Cell Death Discovery |
| title | Cannabichromene: integrative modulation of apoptosis, ferroptosis, and endocannabinoid signaling in pancreatic cancer therapy |
| title_full | Cannabichromene: integrative modulation of apoptosis, ferroptosis, and endocannabinoid signaling in pancreatic cancer therapy |
| title_fullStr | Cannabichromene: integrative modulation of apoptosis, ferroptosis, and endocannabinoid signaling in pancreatic cancer therapy |
| title_full_unstemmed | Cannabichromene: integrative modulation of apoptosis, ferroptosis, and endocannabinoid signaling in pancreatic cancer therapy |
| title_short | Cannabichromene: integrative modulation of apoptosis, ferroptosis, and endocannabinoid signaling in pancreatic cancer therapy |
| title_sort | cannabichromene integrative modulation of apoptosis ferroptosis and endocannabinoid signaling in pancreatic cancer therapy |
| url | https://doi.org/10.1038/s41420-025-02674-8 |
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