Entry #: 39
Date: 27 February 2018
Section: Phenolics – oleuropein
Topic: Oleuropein in combination with cisplatin in HepG2 cells
Type: In vitro model

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D. Elizabeth McCord, Nancy B. Ray and Tom C. Karagiannis


Oleuropein potentiates anti-tumor activity of cisplatin against HepG2 through affecting proNGF/NGF balance


Sherif et al

Citation / Year

(1) / 2018


Oleuropein, cisplatin, hepatocellular carcinoma, HepG2 cells, nerve growth factor


Hepatocellular carcinoma is a relatively common malignancy with a high rate of mortality with metastasis and development of drug resistance, representing major clinical problems (2-4). The alkylating agent, cisplatin, is an important anticancer chemotherapeutic with a long history of clinical use as a frontline agent (5, 6). One of the important aspects of cancer chemotherapy is the use of combination therapies to potentially augment cytotoxicity. The represents the major aim of this study in which combinations the major olive phenolic, oleuropein with cisplatin were investigated for cytotoxic effects in a cell culture model of hepatocellular carcinoma using HepG2 cells. Oleuropein, which is well-known to possess potent antioxidant and anti-inflammatory effects, was chosen since it has been shown to possess cytotoxic effects in a variety of models of human cancer.

Key points and implications

The studies performed in this work represent classical cell culture experiments involving assessment of cell viability, oxidative stress (nitric oxide), levels of pro nerve growth factor (associated with apoptosis), and nerve growth factor (associated with cellular survival) , quantitative real-time polymerase chain reaction to measure gene expression changes. Hepatocellular carcinoma, HepG2, were typically treated for 48 hours with various concentrations of either cisplatin (0-100 μM), or oleuropein (0-400 μM); in selected experiments cell were treated with 50 μM cisplatin in combination with varying concentrations of oleuropein. As anticipated, cisplatin and oleuropein reduced the survival of HepG2 cells, and importantly, the findings highlight that oleuropein augments cisplatin-induced cytotoxicity. Similarly, using gene expression studies oleuropein was shown to modulate cisplatin-induced apoptosis, as indicated by increased expression of pro-apoptotic caspase-3. Similarly, both cisplatin and oleuropein were both shown to decrease the expression of matrix metalloproteinase-7, for which it has been shown that expression is associated with poor survival. Further cisplatin was shown to decrease the cellular levels of nitric oxide, and to up-regulate pro nerve growth factor and down-regulate nerve growth factor. The findings indicated that these effects were augmented in combination with oleuropein. Overall, these findings highlight the feasibility of potentially combining conventional chemotherapeutic agents with bioactive dietary compounds in the context of cancer therapy.

Related publications

  1. I. O. Sherif, M. M. H. Al-Gayyar, Oleuropein potentiates anti-tumor activity of cisplatin against HepG2 through affecting proNGF/NGF balance. Life sciences, (2018).
  2. P. D. S. Marcon, C. V. Tovo, D. A. Kliemann, P. Fisch, A. A. de Mattos, Incidence of hepatocellular carcinoma in patients with chronic liver disease due to hepatitis B or C and coinfected with the human immunodeficiency virus: A retrospective cohort study. World journal of gastroenterology 24, 613-622 (2018).
  3. M. Le Grazie, M. R. Biagini, M. Tarocchi, S. Polvani, A. Galli, Chemotherapy for hepatocellular carcinoma: The present and the future. World journal of hepatology 9, 907-920 (2017).
  4. G. Mazzoccoli, L. Miele, J. Oben, A. Grieco, M. Vinciguerra, Biology, Epidemiology, Clinical Aspects of Hepatocellular Carcinoma and the Role of Sorafenib. Current drug targets 17, 783-799 (2016).
  5. J. A. Gottlieb, B. Drewinko, Review of the current clinical status of platinum coordination complexes in cancer chemotherapy. Cancer chemotherapy reports 59, 621-628 (1975).
  6. O. B. Ellington, Cis-platinum: a brief review of its use, and nursing guidelines. Cancer nursing 1, 403-406 (1978).