Cisplatin is a well-known anticancer drug frequently used for treating solid tumors, including ovarian, testicular, bladder, and cervical tumors. However, usage of cisplatin has been limited because of its adverse effects, particularly nephrotoxicity. Therefore, the present study sought to investigate the protective effect of formononetin against cisplatin-induced cytotoxicity in LLC-PK1 pig kidney epithelial cells as well as the anticancer effect of cisplatin in three different human cervical cancer cell lines, including HeLa, SiHa, and CaSKi cells. We first demonstrated that formononetin strongly prevented cisplatin-induced LLC-PK1 cell death. Although formononetin had no anticancer effect, it did not interrupt the anticancer effect of cisplatin in human cervical carcinoma cell lines. Furthermore, the treatment with formononetin reduced reactive oxygen species (ROS) accumulation and chromatin condensation. The percentage of Annexin V-positive cells also increased following cisplatin treatment. Finally, formononetin-inhibited c-Jun N-terminal kinase (JNK) phosphorylation, cleavage of caspase-8 and caspase-3, and the ratio of Bax to Bcl-2 increased with cisplatin. Taken together, these findings suggest that formononetin may be a possible option to prevent nephrotoxicity induced by cisplatin during treatment for cervical cancer.

Breast cancer is the most common malignancy in both developing and developed countries. In this study, we simultaneously analyzed nine constituent compounds from Spatholobi Caulis (gallic acid, (−)-gallocatechin, 3,4-dihydroxybenzoic acid, procyanidin B1, 3,4-dihydroxybenzaldehyde, catechin, procyanidin B2, epicatechin, and (−)-epicatechin gallate) and examined their anticancer effects on MCF-7 and MDA-MB-231 human breast cancer cells. The experimental results indicated that the gallic acid showed the strongest cytotoxic effect on MCF-7 cells among tested compounds whilst most of samples did not express inhibitory effect on viability of MDA-MB-231 cells, except for 70% ethanol extract of S. Caulis. Thus, gallic acid was chosen to extend anticancer mechanism study on MCF-7 cells. Our data showed that the gallic acid induced apoptotic MCF-7 cell death through both extrinsic and intrinsic pathways, which increased the expression of cleaved caspase-7, -8, and -9, Bax and p53, but reduced the expression of Bcl-2 and poly (ADP-ribose) polymerase (PARP). In addition, the network pharmacological analysis pointed out that the p53, mitogen-activated protein kinase (MAPK), estrogen, and Wnt signaling pathways have a great correlation with the targets of gallic acid. This study suggested that gallic acid is a bioactive component of S. Caulis with potential to be used in chemotherapy for breast cancer.