Cancer is known as a serious disease that impacts human life, and countless scholars have been trying to develop a cure for it. According to 2018 statistics, despite being outside the top 10 of newly diagnosed cancers, ovarian cancer is the fifth lethal cancer among women in the USA [25]. Ovarian cancer is usually at an advanced stage at the time of diagnosis, and it is also recognized as a cancer that is difficult to treat due to the development of drug resistance. Thus far, numerous studies have been published on ovarian cancer, many related to traditional surgery and chemotherapy. More recently, the scope of interest has been expanding into targeted therapy and hormone therapy. The presence of metastasis is a major obstacle that significantly impacts treatment and recurrence.
With respect to metastasis, the processes of cell adhesion, attachment, invasion and modification of filopodia are essential. Cytoskeletal and intercellular interactions between cancer cells and non-cancer, host stromal cells are also required [11]. In this step, multiple actin-binding proteins have a major role in the rearrangement of the actin-cytoskeleton complex of cells, and are essential to cancer cell invasion and cell rigidity modification [26]. The fascin pathway is important to cell structure and function [26], and represents a significant signaling pathway that is associated with cellular interactions during cancer progression [27, 28]. Fascin is an actin-binding protein and known to exist in the nervous system, vascular endothelial cells, genitourinary system, and gastrointestinal system. Fascin functions by producing filopodia and lamellopodia [27], and it is essential to cellular invasion, as it affects extracellular matrix cytoplasmic microfilaments. Several studies have reported a relationship between cancer occurrence and fascin expression. High fascin expression has been associated with increased mortality in breast, colorectal, and pancreatic cancers, and with metastasis in colorectal and gastric cancers [12, 13]. Recent studies have suggested that fascin is highly expressed in ovarian cancer cells, it is associated with metastasis, and may be a prognostic factor [14]. High fascin expression in cancer is associated with worse prognosis and a shorter disease-free interval [12]. The suppression of fascin may represent a key protein in cancer treatment and recurrence.
Curcumin (diferuloylmethane) is known as an Indian spice with a yellowish color that is derived from the Curcuma longa Lin plant [15]. People have been consuming curry for a long time, and it is widely enjoyed as a healthy food. Actually, curcumin exhibits anti-inflammatory, antioxidant, and anti-infective properties and its use is being investigated. Recent numerous studies revealed the anticancer properties of curcumin involve the inhibition of cancer cell adhesion and migration, which are essential for cancer cell survival [16–19]. Its anticancer effect is related to the attenuation of several signaling mechanisms, including the inhibition of transcription factors, proteases, protein kinases, inflammatory cytokines, and their respective signaling pathways [24]. Many investigators have demonstrated protective effects of curcumin on cancer stem cells from colorectal, pancreatic, breast, brain, and head and neck cancers [20–23].
Several previous reports have indicated that curcumin has efficacy in the treatment of ovarian cancer. Koroth et al. demonstrated that the curcumin derivatives, ST03 and ST08, induced ovarian cancer cell death by activating the intrinsic apoptotic pathway [29]. Liu et al. suggested that curcumin reduces cancer cell viability and enhances protective autophagy of ovarian cancer cells by inhibiting the AKT/mTOR/p70S6K signaling pathway [30]. McGuire et al reported that fascin inhibition blocked ovary cancer metastasis in ovarian cancer cells and stromal cells [11]. At the present time, there are no studies regarding the effects of curcumin and fascin in ovarian cancer.
Our goal was to determine the effects of curcumin in ovarian cancer and the fascin pathway, affecting cellular interactions that are essential for recurrence and metastasis of cancer cells. In the SKOV3 ovarian cancer cell line, which was treated with curcumin in an MTS assay, exposure to higher concentrations and greater exposure time resulted in decreased viability. Curcumin had a toxic effect on the ovarian cancer cells and it was clear that it affected cell survival. In this study, we decided to conduct experiments with less toxic concentrations, so that we set the minimum exposure concentration at 10 µM and exposure time at 6 hours. Through cell attachment assays, the longer the curcumin exposure time, the higher the exposure concentration, and a statistically significant decrease in cell adhesion was observed. Based on the decrease in fascin density when the curcumin exposure time was longer, western blot analysis revealed that curcumin is involved in fascin inhibition and pSTAT3 levels analyzed through ELISA appeared similar to that of fascin. Therefore, curcumin has an inhibitory effect on STAT3 through the JAK/STAT3 signaling pathway, and STAT3 inhibition is also involved with the inhibition of fascin. The cell migration assay also indicated that cell closures were reduced when exposed to high concentrations of curcumin. Curcumin exposure also affected the formation of architecture and filopodia in the ovarian cancer cells. A higher curcumin exposure concentration and exposure time resulted in a greater effect.