## 4 Discussion
### Selectivity Index of S. triloba for U2 OS and SKOV3 Cells  
Hek-293 cells (normal human embryonic kidney cells) were used to determine the SI of _S. triloba_ treatment for both U2 OS and SKOV3 cells. Between the two cell lines, _S. triloba_ was 2.5 times more selective for U2 OS cells than SKOV3 cells. Although _S. triloba_ displayed moderate selectivity for U2 OS cells, that of SKOV3 was relatively low. This difference in selectivity between U2 OS and SKOV3 cell lines could be owed to the fact that the two cell lines are distinct and represent different type of cancer. It is suggested that SI values greater than one are favorable for treatment since they display greater therapeutic effect, with minimal toxicity to non-cancerous cells [60]. The relatively modest SI values observed for both U2 OS and SKOV3 cells treated with _S. triloba_ could be attributed to the fact that in addition to therapeutic compounds, the crude extract probably contains some toxic compounds, and chemical profiling to identify and remove such compounds is recommended [34]. Moreover, it is argued that selectivity indices can display significant variability due to their dependence on IC\({}_{50}\) values which could in turn fluctuate based on differences in cell type, cell developmental stages, as well as initial cell densities [61]. Indeed, although Hek-293 cells used for SI calculation in this study are considered a common standard for normal human cells, they are reported to be tumorigenic [31]. Therefore, re-evaluation using a different biosystem(s) it is recommended for herbal drugs with selectivity indices between 1 and 10 [34]. The Combination of S. triloba Acetone Extract and Paclitaxel Exhibits Strong Synergism in SKOV3 Cells  
Drug combinations are a foundational aspect of cancer therapy due to their ability to alleviate the toxicity of chemotherapy as well as prevent drug resistance. The use of two or more drugs in combination facilitates the targeting of multiple oncogenic pathways, eventually leading to either synergistic or additive responses. These responses ultimately permit the realization of high therapeutic effect at reduced dose [62; 63; 64]. A range of combination studies have examined the synergistic effect of combining plant secondary metabolites with clinical chemotherapeutics [65; 66]. When combined with cisplatin, berberine induced both necrotic and apoptotic cell death in OVCAR3 ovarian cancer cell lines [67]; similar observations were noted when the OV2008 human ovarian cancer cell line and their C13 variant (cisplatin resistant) were treated with a combination of curcumin and either cisplatin or oxaliplatin [68]. Furthermore, the green tea polyphenol derivative, epigallocatechin-3-gallate, re-sensitized 3 ovarian cancer cell lines (SKOV3, CAOV3, and C200 cells) to cisplatin by either 3 or more fold [69]. Since paclitaxel is a plant derived terpenoid [70], we thought it appropriate to have it tested in combination with _S. triloba_. Our expectation was that the combined structural complexity between paclitaxel and _S. triloba_ would result in a synergistic effect when tested against SKOV3 cells. In this study, the combination of 19 \(\upmu\)g/mL of acetone extract, and 0.787 \(\upmu\)g/mL of paclitaxel displayed synergy (CI = 0.6415), and yieldedan inhibition effect of 88.33%. We additionally determined the DRI values for each drug at this inhibition point. In a synergistic combination, the DRI provides a measure of the number of folds by which each drug dose can be reduced at a given effect level. DRI values above 1 indicate that the dose of a given drug can be reduced when used in combination. As such, DRI values less than 1 are unfavorable for dose reduction. Our obtained DRI values thus represented favorable dose reduction folds of approximately 28 and 1.6, for _S. triloba_ and paclitaxel respectively [38; 39]. These results imply that _S. triloba_ contains secondary metabolites that could be utilized for adjuvant therapy [71], when combined with clinical chemotherapeutics. _S.