# The Impact of Sulforapahane on Sex-Specific Conditions and Hormone Balance: A Comprehensive Review
## 6 SF Synergies with Cancer Treatments: Breast, Ovarian, Cervical, and Prostate
The triple combination (SF + GE + NaB) had the greatest impact followed by SF + GE, SF + NaB, and GE + NaB, which were integrally more efficacious than singly administered compounds or control in suppressing cell proliferation, promoting apoptosis and inducing cell cycle arrest. Additionally, the combination treatments administered at dietary levels had enhanced effects in modulating epigenetic chemistry via the down-regulation of key players of DNA methylation, histone deacetylation, histone methylation, and histone acetylation, along with global enzymatic activity changes. Epithelial-mesenchymal transition (EMT) allows cancer cells of an epithelial origin to acquire mesenchymal properties, leading to the progression and development of drug resistance. Use of gefitinib has been associated with the development of EMT as a method of the cells escaping the drug toxicity. [PERSON] and colleagues [182] demonstrated that the addition of SF could overcome gefitinib resistance in a lung adenocarcinoma cell line by inducing dose-dependent antiproliferative effects in both non-resistant and gefitinib-resistant cells, whereas induced cell cycle arrest and cell apoptosis occurred only in the gefitinib-resistant cells. The synergistic effect was mechanistically documented to result from a variety of known SF targets leading to EMT. Other systems have similarly shown \begin{table}
\begin{tabular}{l l l} \hline
**Drug or Modality** & **Cancer Type** & **Reference** \\ \hline TRAIL (TNF-related apoptosis ligand) & prostate & [PERSON] (2014) [176] \\ \hline TRAIL & prostate & [PERSON] (2014) [176] \\ \hline chloroquine & prostate & [PERSON] (2013) [144] \\ \hline biculatamide & prostate & [PERSON] (2016) [135] \\ \hline enzalutamide & prostate & [PERSON] (2016) [135] \\ \hline ganetespib & prostate & [PERSON] (2017) [177] \\ \hline paclitaxel & prostate & [PERSON] (2024) [151] \\ \hline EGCG & prostate & [PERSON] (2010) [178] \\ \hline Vitamin D & prostate & [PERSON] (2023) [179] \\ \hline hydrogen sulfide & prostate & [PERSON] (2011) [180] \\ \hline drug-mediated toxicity & prostate & [PERSON] (2011) [175] \\ \hline TRAIL & prostate & [PERSON] (2020) [181] \\ \hline \end{tabular}
\end{table} 
Table 2: _Cont._the potential of SF to down-regulate the transition to EMT. In a triple negative breast cancer line, a SF-cisplatin combination inhibited stemness (reversion to pluripotent stem call characteristics) and metastatic potential by down-regulating sirtuin-mediated EMT signaling [173]. The combination was strongly synergistic and multifunctional. Among the more mechanistically intriguing synergies is that of an antibiotic ionophore and SF. Salinomycin, a decades-old potassium ionophore isolated from _Streptomyces_ spp. which has long been used in veterinary medicine. Over a decade ago, it was found to be 100 times more potent than paclitaxel against breast cancer stem cells, and then also effective against many other types of cancer, and it also enhances the cytotoxic effects of many conventional chemotherapeutic agents. [PERSON] et al. [183] demonstrated that SF and salinomycin synergistically inhibited proliferation, induced apoptosis, and decreased migration and invasion of human colorectal adenocarcinoma cells. SF and 5-fluorouracil were shown to act synergistically in a highly invasive, triple negative breast cancer cell line by inducing autophagy and premature senescence [172,184]. SF acted synergistically with cisplatin to inhibit ovarian cancer cell proliferation and promote apoptosis in vitro. SF by itself inhibited xenograft tumor growth and progression in vivo in a dose-dependent manner [104].