# 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  
An abundance of peer reviewed studies very credibly document synergies between SF and: (a) existing cancer treatment drugs, (b) pharmaceuticals under development but not yet on the market or in the regulatory pipeline, (c) loosely characterized proprietary mixes such as extracts of fern leaves, and (d) cell lines that are resistant to various cancer drugs and but made more susceptible to them by treating with SF. Notably, the majority of these findings pertain to cancer therapies. Seventy-six papers (and counting) provide evidence in cell lines. Many provide convincing mechanistic evidence for the effects, and some of them use the gold-standard Chou-Talalay technique [159] for demonstrating true synergy. Examples of those pertaining specifically to breast, cervical, ovarian and prostate cancers are listed in Table 2. \begin{table}
\begin{tabular}{l l l} \hline
**Drug or Modality** & **Cancer Type** & **Reference** \\ \hline afimoxifene & breast & [PERSON] (2016) [160] \\ \hline biochanin A & breast & [PERSON] (2024) [161] \\ \hline clofarabine & breast & [PERSON]- (2015) [162] \\ \hline docetaxel & breast & [PERSON] (2017) [163] \\ \hline doxorubicin & breast & [PERSON] (2018) [164] \\ \hline exemestane & breast & [PERSON] and [PERSON] (2013) [88] \\ \hline gemcitabine & breast & [PERSON] (2013) [165] \\ \hline genestein & breast & [PERSON] (2018) [166] \\ \hline genestein & breast & [PERSON] (2022) [167] \\ \hline lapatinib & breast & [PERSON] (2015) [168] \\ \hline paclitaxel & breast & [PERSON] (2017) [163] \\ \hline piperine & breast & [PERSON] (2019) [169] \\ \hline sodium butyrate & breast & [PERSON] (2022) [167] \\ \hline thymoquinone & breast & [PERSON] (2019) [169] \\ \hline withafterin A & breast & [PERSON] (2018) [170] \\ \hline doxorubicin & breast & [PERSON] (2019) [171] \\ \hline
5-fluorouracilacil & breast (TNBC) & [PERSON] (2018) [172] \\ \hline cisplatin & breast (TNBC) & [PERSON] (2021) [173] \\ \hline doxorubicin & breast (TNBC) & [PERSON] (2023) [174] \\ \hline eugenol & cervical & [PERSON] (2012) [96] \\ \hline cisplatin & ovarian & [PERSON] (2020) [101] \\ \hline cisplatin & ovarian & [PERSON] (2018) [104] \\ \hline EGCG & ovarian & [PERSON] (2013a) [99] \\ \hline EGCG + cisplatin & ovarian & [PERSON] (2013b) [100] \\ \hline cisplatin & prostate & [PERSON] (2011) [175] \\ \hline taxol (paclitaxel) & prostate & [PERSON] (2011) [175] \\ \hline \end{tabular}
\end{table} 
Table 2: Synergy of sulforaphane with drug or treatment (e.g., phytochemical). [PERSON] et al. [161] describe synergy between SF + biochanin A (BCA), which is an isoflavone found in _Trifolium pratense_ (red clover). The combination suppressed cancer in an in vivo breast cancer system by reducing cell proliferation and promoting apoptosis, causing cell cycle arrest and down-regulating ERK-1/2 and other cell proliferation factors. [PERSON] et al. [174] examined the effects of SF + doxorubicin on triple-negative breast cancer in an animal model. Doxorubicin is a long-used chemotherapy drug that arrests or slows cancer cell growth by blocking the enzyme topoisomerase 2. The synergistic combination reduced primary mammary tumors in a mouse model, increased doxorubicin nuclear accumulation, and exhibited cardio-, nephro- and hepato-protective effects. An in vitro study by [PERSON] and [PERSON] [167] targeted epigenetic mechanisms in breast cancer. Sodium butyrate (NaB) is a short-chain fatty acid produced by gut bacteria which has a variety of antineoplastic properties, including the inhibition of histone deacetylase (HDAC). The phytochemical genistein (GE) is a potent inhibitor of DNA methyltransferases (DNMTs), which are epigenetic enzymes controlling DNA methylation and hence its transcriptional activity. SF, among its many other mechanisms, is an HDAC inhibitor.