The natural isoflavone Biochanin‐A synergizes 5‐fluorouracil anticancer activity in vitro and in vivo in Ehrlich solid‐phase carcinoma model

Abstract

Isoflavones are considered one of the most extensively studied plant-derived phytoestrogenic compounds. Of these, Biochanin A (Bio-A), a natural isoflavone abundant in cabbage, alfalfa, and red clover, has drawn a lot of attention. As reported in multiple studies, Bio-A possesses a promising anticancer activity against estrogen receptor-positive (ER+) breast cancer. The current study investigated the working hypothesis that Bio-A could synergistically enhance the potency of 5-fluorouracil(5-FU) in ER+ breast cancer. The hypothesis was tested both in vitro on hormone receptor-positive (MCF-7) and triple-negative breast cancer cells (MDA-MB231).Additionally, in vivo studies were performed in the Ehrlich solid-phase carcinoma mouse model. The in vitro cytotoxicity studies revealed that Bio-A synergistically increased the potency of 5-FU in both MCF-7 and MDA-MB231 cell lines. The synergistic effect of 5-FU/Bio-A combination was verified in vivo. The combination therapy (where 5-FU was used at one fourth its full dose) led to a significant 75% reduction in tumor volume after two treatment cycles. This was in addition to producing a significant 2.1-fold increase in tumor necrosis area% compared to mocktreated control. In conclusion, the current study presents the first preclinical evidence

Comprehensive exploration of Biochanin A as an oncotherapeutics potential in the treatment of multivarious cancers with molecular insights

“…For example, the combined effect of sorafenib and BCA was tested in a hepatocellular carcinoma cell line, including HepG2, Huh-7, and SNU-449 cells and the results demonstrated the mixture of these compounds prevented cell proliferation by arresting the cell cycle at the pre-G and G0/G1 phases and decreasing cyclin D1 protein level and the Bcl-2/Bax ratio (Youssef et al, 2016). Additionally, BCA is effective against lung cancer with a resulting in a 2.1-fold increase in tumor necrosis area (Mahmoud et al, 2022). Even more impressively, this combination resulted in a 75% reduction in tumor volume after two treatment cycles in the ehrlich solid-phase cancer mouse model (Mahmoud et al, 2022).…”

Mechanisms behind the pharmacological application of biochanin-A: a review

“…Biochanin-A has shown synergism with 5-fluorouracil (5FU) in oestrogen receptor (ER) positive breast cancer cell lines such as triple-negative breast cancer cells, MDA-MB231 and MCF7. The combination of 5FU and biochanin-A producing a synergistic anti-tumour effect partly attributed to the inhibitory capability of biochanin-A through ER-α/Akt (Mahmoud et al, 2022). The mechanism of action of biochanin-A in breast cancer by dephosphorylation of HER-2 receptor and MAPK or ERK1/2 causing blockade of cancer cell development, growth, metastasis, and mitogenesis, the inhibition of Akt phosphorylation and downregulation of mTOR signals that disrupt the cell cycle, the inhibition of NF-kB and interrupted transcription and blockade of topoisomerase-II and DNA replication is depicted in Figure 2.…”

Antiangiogenic drugs in combination with seaweed fucoidan: A mechanistic in vitro and in vivo study exploring the VEGF receptor and its downstream signaling molecules in hepatic cancer

“…Medicinal plant-based herbal products have gained a lot of momentum in pursue of safer as well as more efficient anticancer therapies. They are mainly used as adjuvant therapies to reduce the toxic side effect of standard chemotherapies (Atashrazm et al, 2015;Bonam et al, 2018;Mahmoud et al, 2022). Natural polysaccharides obtained from algae and marine plants have drawn a lot of attention in recent years owing to their potential anti-cancer effect as well as their diverse biological activities (Atashrazm et al, 2015).…”