## 1 Introduction  
Ovarian cancer is the second most common gynecologic cancer with an estimated 21,750 new cases and 13,940 mortalities predicted to occur across the United States in 2020 [1]. Globally, there are 239,000 new cases and 152,000 deaths due to ovarian cancer every year [2]. More than two-thirds of all women diagnosed with epithelial ovarian cancer will die from the disease, a fact that has not changed considerably in the last three decades. The lack of effective screening results in 50% to 60% of patients being diagnosed with advanced stage disease [3]. Although treatment for ovarian cancer, including surgery and platinum-based chemotherapy, has improved, the 5- and 10-year survival rates of advanced ovarian cancer stages were only 32% and 15%, respectively [4]. Approximately 80% of ovarian cancer patients initially respond to chemotherapy, but more than 60% of these patients who receive standard treatment will relapse and die due to chemoresistance [5]. Thus, recent research has focused on natural polyphenol compounds, which have been shown to double the survival time of the cancer patients in this century [6].  
Nuts are known for their health benefits, including anti-cardiovascular disease and anti-oxidative properties. Recently, a significant inverse association between nut consumption and overall mortality was observed by The National Institutes of Health-American Association of Retired Persons (AARP) Diet and Health Study. This study showed that nut consumption was significantly associated with reduced risk of cancer and cardiovascular, respiratory, infectious, renal, and liver disease mortality [7]. [PERSON] et al. found that walnut consumption could suppress growth and survival of breast cancers in mice [8]. Recent reports show that phenols have the ability to inhibit tumors [9]. It has been reported that polyphenic compounds, a large family of natural compounds abundant in nuts, have been associated with a possible reduced risk of colon cancer [10], breast cancer [11] and melanoma [12].  
Chinese hickory (_Carya cathayensis_), which has been commercially cultivated for more than 500 years, is a native nut species of Zhejiang Province in China. Our previous research showed that, like other nuts, Chinese hickory nuts are rich in polyphenols (78.28 \(\pm\) 0.378 mg gallic acid equivalents/g) [13]. However, there is no report on the anti-tumor function of Chinese hickory polyphenols. The flesh of the walnut seed is surrounded by a brown leathery coating, called the skin or the seed coat, which protects the walnut kernel from oxidation and microbial contamination. Component analysis shows that polyphenols are mainly present in the skin of nuts [14; 15]. Research on these polyphenols will help the comprehensive utilization of Chinese hickory, but there is little research on the seed skin of Chinese hickory nuts to evaluate anti-tumor activity. The purpose of this study was to investigate the inhibitory effects of Chinese hickory seed skin polyphenols (CHSP) on ovarian cancer cell lines. Furthermore, the inhibitory mechanism of CHSP on ovarian cancer cells was also analyzed by using Western blot and enzyme-linked immunoassay (ELISA).