17β-estradiol Enhances 5-Fluorouracil Anti-Cancer Activities in Colon Cancer Cell Lines
Background: 5-Fluorouracil (5-FU) represents one of the major constituents of chemotherapy combination regimens in colon cancer (CRC) treatments; however, this regimen is linked with severe adverse effects and chemoresistance. Thus, developing more efficient approaches for CRC is urgently needed to...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Medical Sciences |
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| Online Access: | https://www.mdpi.com/2076-3271/10/4/62 |
| _version_ | 1797456418165489664 |
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| author | Amani A. Mahbub |
| author_facet | Amani A. Mahbub |
| author_sort | Amani A. Mahbub |
| collection | DOAJ |
| description | Background: 5-Fluorouracil (5-FU) represents one of the major constituents of chemotherapy combination regimens in colon cancer (CRC) treatments; however, this regimen is linked with severe adverse effects and chemoresistance. Thus, developing more efficient approaches for CRC is urgently needed to overcome these problems and improve the patient survival rate. Currently, 17β-estradiol (E2) has gained greater attention in colon carcinogenesis, significantly lowering the incidence of CRC in females at reproductive age compared with age-matched males. Aims: This study measured the effects of E2 and/or 5-FU single/dual therapies on cell cycle progression and apoptosis against human HT-29 female and SW480 male primary CRC cells versus their impact on SW620 male metastatic CRC cells. Methods: The HT-29, SW480, and SW620 cells were treated with IC<sub>50</sub> of E2 (10 nM) and 5-FU (50 μM), alone or combined (E+F), for 48 h before cell cycle and apoptosis analyses using flow cytometry. Results: The data here showed that E2 monotherapy has great potential to arrest the cell cycle and induce apoptosis in all the investigated colon cancer cells, with the most remarkable effects on metastatic cells (SW620). Most importantly, the dual therapy (E+F) has exerted anti-cancer activities in female (HT-29) and male (SW480) primary CRC cells by inducing apoptosis, which was preferentially provoked in the sub-G<sub>1</sub> phase. However, the dual treatment showed the smallest effect in SW620 metastatic cells. Conclusion: this is the first study that demonstrated that the anti-cancer actions of 17β-estradiol and 5-Fluorouracil dual therapy were superior to the monotherapies in female and male primary CRC cells; it is proposed that this treatment strategy could be promising for the early stages of CRC. At the same time, 17β-estradiol monotherapy could be a better approach for treating the metastatic forms of the disease. Nevertheless, additional investigations are still required to determine their precise therapeutic values in CRC. |
| first_indexed | 2024-03-09T16:07:36Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-3271 |
| language | English |
| last_indexed | 2024-03-09T16:07:36Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medical Sciences |
| spelling | doaj.art-ce8f3e4fa49d4d2380a1e777745be8c12023-11-24T16:34:32ZengMDPI AGMedical Sciences2076-32712022-10-011046210.3390/medsci1004006217β-estradiol Enhances 5-Fluorouracil Anti-Cancer Activities in Colon Cancer Cell LinesAmani A. Mahbub0Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, P.O. Box 715, Makkah 21955, Saudi ArabiaBackground: 5-Fluorouracil (5-FU) represents one of the major constituents of chemotherapy combination regimens in colon cancer (CRC) treatments; however, this regimen is linked with severe adverse effects and chemoresistance. Thus, developing more efficient approaches for CRC is urgently needed to overcome these problems and improve the patient survival rate. Currently, 17β-estradiol (E2) has gained greater attention in colon carcinogenesis, significantly lowering the incidence of CRC in females at reproductive age compared with age-matched males. Aims: This study measured the effects of E2 and/or 5-FU single/dual therapies on cell cycle progression and apoptosis against human HT-29 female and SW480 male primary CRC cells versus their impact on SW620 male metastatic CRC cells. Methods: The HT-29, SW480, and SW620 cells were treated with IC<sub>50</sub> of E2 (10 nM) and 5-FU (50 μM), alone or combined (E+F), for 48 h before cell cycle and apoptosis analyses using flow cytometry. Results: The data here showed that E2 monotherapy has great potential to arrest the cell cycle and induce apoptosis in all the investigated colon cancer cells, with the most remarkable effects on metastatic cells (SW620). Most importantly, the dual therapy (E+F) has exerted anti-cancer activities in female (HT-29) and male (SW480) primary CRC cells by inducing apoptosis, which was preferentially provoked in the sub-G<sub>1</sub> phase. However, the dual treatment showed the smallest effect in SW620 metastatic cells. Conclusion: this is the first study that demonstrated that the anti-cancer actions of 17β-estradiol and 5-Fluorouracil dual therapy were superior to the monotherapies in female and male primary CRC cells; it is proposed that this treatment strategy could be promising for the early stages of CRC. At the same time, 17β-estradiol monotherapy could be a better approach for treating the metastatic forms of the disease. Nevertheless, additional investigations are still required to determine their precise therapeutic values in CRC.https://www.mdpi.com/2076-3271/10/4/62colon cancer cells17β-estradiol5-Fluorouracilcell cyclesub-G1 phaseapoptosis |
| spellingShingle | Amani A. Mahbub 17β-estradiol Enhances 5-Fluorouracil Anti-Cancer Activities in Colon Cancer Cell Lines Medical Sciences colon cancer cells 17β-estradiol 5-Fluorouracil cell cycle sub-G1 phase apoptosis |
| title | 17β-estradiol Enhances 5-Fluorouracil Anti-Cancer Activities in Colon Cancer Cell Lines |
| title_full | 17β-estradiol Enhances 5-Fluorouracil Anti-Cancer Activities in Colon Cancer Cell Lines |
| title_fullStr | 17β-estradiol Enhances 5-Fluorouracil Anti-Cancer Activities in Colon Cancer Cell Lines |
| title_full_unstemmed | 17β-estradiol Enhances 5-Fluorouracil Anti-Cancer Activities in Colon Cancer Cell Lines |
| title_short | 17β-estradiol Enhances 5-Fluorouracil Anti-Cancer Activities in Colon Cancer Cell Lines |
| title_sort | 17β estradiol enhances 5 fluorouracil anti cancer activities in colon cancer cell lines |
| topic | colon cancer cells 17β-estradiol 5-Fluorouracil cell cycle sub-G1 phase apoptosis |
| url | https://www.mdpi.com/2076-3271/10/4/62 |
| work_keys_str_mv | AT amaniamahbub 17bestradiolenhances5fluorouracilanticanceractivitiesincoloncancercelllines |