Presently, the pathogenesis and clinicopathological properties of OCa have not clearly been expressed [18]. However, some theories have been proposed concerning OCa origination (Figure 1) which includes (1) the gonadotropin theory characterizes over the induction of the epithelium of ovarian surface by hormonal receptors resulting in malignancy, (2) the continuous ovulation theory, in the location of which the cells of ovarian surface epithelium are damaged because of constant ovulation, (3) the origin cells for the majority of epithelial ovarian cancers are not derived from the ovary but mostly originated from the fallopian tube and develop to the ovary and more than it [19]. Regarding hormonal conditions, there is evidence that progesterone and androgens can elevate ovarian epithelium proliferation and subsequently lead to the formation of OCa. Indeed, the increment of androgens and estrogens taggers multiple pro-inflammatory agents resulting in immune activation. During ovulatory occurrences, a great number of molecules are produced, such as chemokines and cytokines, plasminogen activators, prostaglandins, interleukins, bioactive eicosanoids, tumor necrosis factors, collagenases, and a large number of growth factors and immune cells, which all trigger a pro-inflammatory occurrence. Such pro-inflammatory agents, like IL-8, CCL2/MCP-1, and CCL5/RANTES, are induced during each cycle of ovulation; therefore, the continuous ovulation theory recommends that the inflammation accompanied by other physiological situations potentiates OCa progression [20,21]. Plus, it is shown that IL-1β, IL-6, and TNF-α formed by activated immune agents and/or the tumor itself, induce the growth of cancer cells and affect the prognosis and clinical status of the disease via increasing resistance to chemotherapy and stimulating symptoms (e.g., weight loss, anemia, depression, and anorexia) [22]. Oxidative stress, namely reactive nitrogen species (RNS) and reactive oxygen species (ROS), are another factor involved in many pathological conditions, such as OCa, by genetic instability enhancement, angiogenesis promotion, and abnormality in cell proliferation [23,24]. Exogenous agents, like hypoxia, infection, and chronic inflammation, are among the main sources of oxidative stress [25]. Mounting evidence has demonstrated that ROS can modulate the biogenesis and expression of microRNAs by epigenetic alterations, regulating biogenesis course, and transcription factors [26]. MicroRNAs, as noncoding RNAs, have a role in chemoresistance, carcinogenesis, proliferation, apoptosis, cell cycle, invasion, and metastasis. Impairments of microRNAs can lead to the onset and progression of OCa [27]. Possibly, the most important feature of any cancer is genetic changes that mediate the development and progression of tumors [28]. In this line, it is revealed that the presence of mutations in PTEN (Phosphatase and tensin homolog), P53, BRCA(Breast Cancer)1, and BRCA2 genes, and tumor suppressor factors can develop OCa (Figure 2) [29,30,31]. 

Curcumin (CUR) is characterized as a yellow and hydrophobic herbal component that is originated from the turmeric plant (Curcuma longa L. Zingiberaceae) [32]. Growing evidence has shown some positive effects of CUR in medicine, such as anti-tumor, anti-inflammatory, anti-oxidative, immunoregulatory, anti-fungus, and anti-bacterial features [33,34], such as breast, ovarian, prostate, gastric, colorectal, pancreatic, and cervical cancers [35,36,37,38]. Regarding anti-cancer mechanisms of CUR, it has to be said that several signaling pathways are affected by that, for example, JAK (Janus Activated Kinase)/STAT (signal transducer and activator), PI3K (Phosphoinositide 3-kinases)/Akt, MAPK (mitogen-activated protein kinase), NF-ĸB, p53, Wnt/β-catenin, and apoptosis-related signaling (Figure 3). Furthermore, CUR can suppress epithelial-mesenchymal transition (EMT), angiogenesis, proliferation, metastasis, and invasion of the tumor by modulating the expression of non-coding RNA (ncRNA) associated with the tumor [39,40,41,42]. In the study of Shi et al., it was revealed that CUR can considerably suppress the growth and stimulate apoptosis in human OCa cell line Ho-8910. In their research, the use of 40 μM CUR caused a reduction in pro-caspase-3, Bcl-X_L, and Bcl-2, whereas Bax and p53 levels were elevated in the treated cells with CUR [38]. Triggering AMP-activated protein kinase (AMPK), which stimulates cell apoptosis and inhibits cell proliferation in several cancers, in a p38-dependent way is another mechanism of CUR action in ovarian cancer cells CaOV3 [43]. In an animal investigation on OCa, it was manifested that CUR can dramatically suppresses STAT3 and NF-ĸB signaling pathways [44]. Liu et al. have pointed out that CUR can stimulate human OCa cell autophagy through AKT/mTOR (mammalian target of rapamycin)/p70S6K pathway suppression [45]. Despite these, the clinical application of CUR has been limited owing to its instability and low water solubility, which in turn give rise to poor bioavailability of CUR in cancerous cells. Attempts toward elevating the therapeutic effectiveness of Cur have been carried out through various techniques [46]. An in vivo and in vitro investigation showed that nanocurcumin in combination with cisplatin, a common treatment for OCa, could lead to a remarked reduction of the weight and volume of ovarian tumors. In addition, this treatment decreased PI3K, JAK, TGF-β, Ki67 expression, and Akt phosphorylation [51]. Hu et al. (2020) demonstrated that the use of Docetaxel curcumin/methoxy poly (ethylene glycol)-poly (L-lactic acid) (MPEG-PLA) copolymers nanomicelles cause the Suppression of tumor proliferation and angiogenesis (Table 1). The study of Bondi et al. (2017) concluded that biocompatible Lipid nanoparticles as carriers improved curcumin efficacy in ovarian cancer treatment and caused the Reduction of cell colony survival, inhibition of tumor growth, and apoptosis induction (Table 1). Dendrosomal nano-curcumin caused the reduction of cancer cell viability, a decrease of LncRNAs expression of H19 and HOTAIR, and an increase in the expression of MEG3 LncRNA and Bcl2 protein (Table 1). The study of Sandhiutami et al. (2021) showed that co-use of curcumin nanoparticles and Cisplatin caused the Decrease of ovarian tumor weight and volume, reduction of PI3K, TGF-β, JAK, and Ki67 expression, Akt and STAT3 phosphorylation, and decrease of IL-6 level (Table 1). In general, Curcumin is an efficient agent with anti-tumor, antioxidant, and anti-inflammatory activities. The main mechanisms of action by which curcumin exhibits its unique anticancer activity include inducing apoptosis and inhibiting proliferation and invasion of tumors by suppressing a variety of cellular signaling pathways.