Manar F Atoum, Foad E Alzoughool, Zainab A Al-Mazaydeh, Majdoleen S Rammaha, Lubna H Tahtamouni
{"title":"维生素B12通过激活半胱天酶和靶向肌动蛋白细胞骨架增强1,25-二羟基维生素D3的抗肿瘤活性。","authors":"Manar F Atoum, Foad E Alzoughool, Zainab A Al-Mazaydeh, Majdoleen S Rammaha, Lubna H Tahtamouni","doi":"10.3233/TUB-211536","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is an effective anticancer agent, and when combined with other agents it shows superior activities. Vitamin B12 has been shown to contribute to increasing the effectiveness of anticancer drugs when used in combination. Thus, the current study aimed at investigating the anticancer potential of the combination of 1,25(OH)2D3 and vitamin B12.</p><p><strong>Methods: </strong>MTT assay was used to determine the cytotoxic activity of combining 1,25(OH)2D3 and vitamin B12 against six different cancer cell lines and one normal cell line. The surviving fraction after clonogenic assay was measured, and the effects of 1,25(OH)2D3/B12 combination on the activity of different caspases, cell adhesion, actin cytoskeleton, cell morphology, and percentage of polarized cells were evaluated.</p><p><strong>Results: </strong>Vitamin B12 did not cause cytotoxicity, however, it enhanced the cytotoxicity of 1,25(OH)2D3 against cancer cells. The cytotoxic effects of 1,25(OH)2D3 and its combination with vitamin B12 was not evident in the normal mammary MCF10A cell line indicating cancer cell-specificity. The cytotoxic effects of 1,25(OH)2D3/B12 combination occurred in a dose-dependent manner and was attributed to apoptosis induction which was mediated by caspase 4 and 8. Moreover, 1,25(OH)2D3/B12-treated cells showed enhanced inhibition of clonogenic tumor growth, reduced cell adhesion, reduced cell area, reduced percentage of cell polarization, and disorganized actin cytoskeleton resulting in reduced migratory phenotype when compared to cells treated with 1,25(OH)2D3 alone.</p><p><strong>Conclusion: </strong>1,25(OH)2D3 and vitamin B12 exhibited synergistic anticancer effects against different cancer cell lines. The combination therapy of 1,25(OH)2D3 and vitamin B12 may provide a potential adjunctive treatment option for some cancer types.</p>","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":"17-35"},"PeriodicalIF":0.0000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":"{\"title\":\"Vitamin B12 enhances the antitumor activity of 1,25-dihydroxyvitamin D3 via activation of caspases and targeting actin cytoskeleton.\",\"authors\":\"Manar F Atoum, Foad E Alzoughool, Zainab A Al-Mazaydeh, Majdoleen S Rammaha, Lubna H Tahtamouni\",\"doi\":\"10.3233/TUB-211536\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is an effective anticancer agent, and when combined with other agents it shows superior activities. Vitamin B12 has been shown to contribute to increasing the effectiveness of anticancer drugs when used in combination. Thus, the current study aimed at investigating the anticancer potential of the combination of 1,25(OH)2D3 and vitamin B12.</p><p><strong>Methods: </strong>MTT assay was used to determine the cytotoxic activity of combining 1,25(OH)2D3 and vitamin B12 against six different cancer cell lines and one normal cell line. The surviving fraction after clonogenic assay was measured, and the effects of 1,25(OH)2D3/B12 combination on the activity of different caspases, cell adhesion, actin cytoskeleton, cell morphology, and percentage of polarized cells were evaluated.</p><p><strong>Results: </strong>Vitamin B12 did not cause cytotoxicity, however, it enhanced the cytotoxicity of 1,25(OH)2D3 against cancer cells. The cytotoxic effects of 1,25(OH)2D3 and its combination with vitamin B12 was not evident in the normal mammary MCF10A cell line indicating cancer cell-specificity. The cytotoxic effects of 1,25(OH)2D3/B12 combination occurred in a dose-dependent manner and was attributed to apoptosis induction which was mediated by caspase 4 and 8. Moreover, 1,25(OH)2D3/B12-treated cells showed enhanced inhibition of clonogenic tumor growth, reduced cell adhesion, reduced cell area, reduced percentage of cell polarization, and disorganized actin cytoskeleton resulting in reduced migratory phenotype when compared to cells treated with 1,25(OH)2D3 alone.</p><p><strong>Conclusion: </strong>1,25(OH)2D3 and vitamin B12 exhibited synergistic anticancer effects against different cancer cell lines. The combination therapy of 1,25(OH)2D3 and vitamin B12 may provide a potential adjunctive treatment option for some cancer types.</p>\",\"PeriodicalId\":23364,\"journal\":{\"name\":\"Tumor Biology\",\"volume\":\" \",\"pages\":\"17-35\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Tumor Biology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3233/TUB-211536\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tumor Biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3233/TUB-211536","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
Vitamin B12 enhances the antitumor activity of 1,25-dihydroxyvitamin D3 via activation of caspases and targeting actin cytoskeleton.
Background: 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is an effective anticancer agent, and when combined with other agents it shows superior activities. Vitamin B12 has been shown to contribute to increasing the effectiveness of anticancer drugs when used in combination. Thus, the current study aimed at investigating the anticancer potential of the combination of 1,25(OH)2D3 and vitamin B12.
Methods: MTT assay was used to determine the cytotoxic activity of combining 1,25(OH)2D3 and vitamin B12 against six different cancer cell lines and one normal cell line. The surviving fraction after clonogenic assay was measured, and the effects of 1,25(OH)2D3/B12 combination on the activity of different caspases, cell adhesion, actin cytoskeleton, cell morphology, and percentage of polarized cells were evaluated.
Results: Vitamin B12 did not cause cytotoxicity, however, it enhanced the cytotoxicity of 1,25(OH)2D3 against cancer cells. The cytotoxic effects of 1,25(OH)2D3 and its combination with vitamin B12 was not evident in the normal mammary MCF10A cell line indicating cancer cell-specificity. The cytotoxic effects of 1,25(OH)2D3/B12 combination occurred in a dose-dependent manner and was attributed to apoptosis induction which was mediated by caspase 4 and 8. Moreover, 1,25(OH)2D3/B12-treated cells showed enhanced inhibition of clonogenic tumor growth, reduced cell adhesion, reduced cell area, reduced percentage of cell polarization, and disorganized actin cytoskeleton resulting in reduced migratory phenotype when compared to cells treated with 1,25(OH)2D3 alone.
Conclusion: 1,25(OH)2D3 and vitamin B12 exhibited synergistic anticancer effects against different cancer cell lines. The combination therapy of 1,25(OH)2D3 and vitamin B12 may provide a potential adjunctive treatment option for some cancer types.
期刊介绍：
Tumor Biology is a peer reviewed, international journal providing an open access forum for experimental and clinical cancer research. Tumor Biology covers all aspects of tumor markers, molecular biomarkers, tumor targeting, and mechanisms of tumor development and progression.
Specific topics of interest include, but are not limited to:
Pathway analyses,
Non-coding RNAs,
Circulating tumor cells,
Liquid biopsies,
Exosomes,
Epigenetics,
Cancer stem cells,
Tumor immunology and immunotherapy,
Tumor microenvironment,
Targeted therapies,
Therapy resistance
Cancer genetics,
Cancer risk screening.
Studies in other areas of basic, clinical and translational cancer research are also considered in order to promote connections and discoveries across different disciplines.
The journal publishes original articles, reviews, commentaries and guidelines on tumor marker use. All submissions are subject to rigorous peer review and are selected on the basis of whether the research is sound and deserves publication.
Tumor Biology is the Official Journal of the International Society of Oncology and BioMarkers (ISOBM).
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
