Advances of Plant-derived Natural Products in Ovarian Cancer Therapy

Ovarian cancer is the leading cause of death in the gynaecologic cancers within the UK and US. Presently the standard treatment for ovarian cancer entails the use of chemotherapy drugs paclitaxel and carboplatin after aggressive surgical reduction in order to prolong the patient’s life for multiple years. However, prolonged use of platinum-based chemotherapy often leads to drug resistance, which causes the ovarian cancer patient to relapse and potential death. Therefore there is an urgent medical need for breakthrough drugs with an effective therapeutic impact on ovarian cancer. Phytochemicals (plant-derived natural products) have been used for thousands of years as treatment for various diseases, because of their huge chemical diversity and wide range of biological activities. In this review, the role of phytochemicals as chemo-preventive compounds, potential sources of new drugs for ovarian cancer and the benefits of their adoption as monotherapeutic agents or as chemosensitizers when used in-conjunction with the conventional anti-cancer drugs is highlighted. We will describe the phytochemicals: 1) clinically approved drugs such as paclitaxel and camptothecin including its semi-synthetic derivatives topotecan and irinotecan; 2) currently in clinical trials such as epipodophyllotoxin derivatives etoposide and teniposide, ventfolide, phenoxodiol, and combretastatins; 3) in preclinical trials such as quercetin, baicalein, baicalin, thymoquinone, betulinic acid and tetrandrine; and recently discovered compounds which have high potency (IC50 less than 10 μM) and have been discovered recently (last 15 years). In particular, several new compounds including bufatrienolides, ipomoeassin D, 2'-(R)-O-acetylglaucarubinone, and molvizarin have IC50s lower than 100 nM in ovarian cancer cells and might have different mechanisms of action from those of platinum derivatives/paclitaxel, therefore providing potential ways to attack multidrug resistance in ovarian cancer without jeopardising the patient’s treatment.  Corresponding author: Dr. Wen-Wu Li. E-mail: [email protected] Wen-Wu Li, Okiemute Rosa Johnson-Ajinwo, and Fidelia Ijeoma Uche 82