The onset of this new pandemic has highlighted the numerous critical issues at the organizational level, which involve both national healthcare and the judicial system. Nevertheless, additional investigations are still required to determine their precise therapeutic values in CRC. At the same time, 17β-estradiol monotherapy could be a better approach for treating the metastatic forms of the disease. 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. However, the dual treatment showed the smallest effect in SW620 metastatic cells. 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 1 phase. 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). Methods: The HT-29, SW480, and SW620 cells were treated with IC 50 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. 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. 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. Thus, developing more efficient approaches for CRC is urgently needed to overcome these problems and improve the patient survival rate. 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.
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