TY - JOUR
T1 - Lycopene reduces ovarian tumor growth and intraperitoneal metastatic load
AU - Holzapfel, Nina Pauline
AU - Shokoohmand, Ali
AU - Wagner, Ferdinand
AU - Landgraf, Marietta
AU - Champ, Simon
AU - Holzapfel, Boris Michael
AU - Clements, Judith Ann
AU - Hutmacher, Dietmar Werner
AU - Loessner, Daniela
PY - 2017
Y1 - 2017
N2 - Mutagens like oxidants cause lesions in the DNA of ovarian and fallopian tube epithelial cells, resulting in neoplastic transformation. Reduced exposure of surface epithelia to oxidative stress may prevent the onset or reduce the growth of ovarian cancer. Lycopene is well-known for its excellent antioxidant properties. In this study, the potential of lycopene in the prevention and treatment of ovarian cancer was investigated using an intraperitoneal animal model. Lycopene prevention significantly reduced the metastatic load of ovarian cancer-bearing mice, whereas treatment of already established ovarian tumors with lycopene significantly diminished the tumor burden. Lycopene treatment synergistically enhanced anti-tumorigenic effects of paclitaxel and carboplatin. Immunostaining of tumor and metastatic tissues for Ki67 revealed that lycopene reduced the number of proliferating cancer cells. Lycopene decreased the expression of the ovarian cancer biomarker, CA125. The anti-metastatic and antiproliferative effects were accompanied by down-regulated expression of ITGA5, ITGB1, MMP9, FAK, ILK and EMT markers, decreased protein expression of integrin a5 and reduced activation of MAPK. These findings indicate that lycopene interferes with mechanisms involved in the development and progression of ovarian cancer and that its preventive and therapeutic use, combined with chemotherapeutics, reduces the tumor and metastatic burden of ovarian cancer in vivo.
AB - Mutagens like oxidants cause lesions in the DNA of ovarian and fallopian tube epithelial cells, resulting in neoplastic transformation. Reduced exposure of surface epithelia to oxidative stress may prevent the onset or reduce the growth of ovarian cancer. Lycopene is well-known for its excellent antioxidant properties. In this study, the potential of lycopene in the prevention and treatment of ovarian cancer was investigated using an intraperitoneal animal model. Lycopene prevention significantly reduced the metastatic load of ovarian cancer-bearing mice, whereas treatment of already established ovarian tumors with lycopene significantly diminished the tumor burden. Lycopene treatment synergistically enhanced anti-tumorigenic effects of paclitaxel and carboplatin. Immunostaining of tumor and metastatic tissues for Ki67 revealed that lycopene reduced the number of proliferating cancer cells. Lycopene decreased the expression of the ovarian cancer biomarker, CA125. The anti-metastatic and antiproliferative effects were accompanied by down-regulated expression of ITGA5, ITGB1, MMP9, FAK, ILK and EMT markers, decreased protein expression of integrin a5 and reduced activation of MAPK. These findings indicate that lycopene interferes with mechanisms involved in the development and progression of ovarian cancer and that its preventive and therapeutic use, combined with chemotherapeutics, reduces the tumor and metastatic burden of ovarian cancer in vivo.
KW - Antioxidant
KW - Humanized animal model
KW - Hydrogels
KW - Lycopene
KW - Ovarian cancer
UR - http://www.scopus.com/inward/record.url?scp=85021212203&partnerID=8YFLogxK
M3 - Article
C2 - 28670494
AN - SCOPUS:85021212203
SN - 2156-6976
VL - 7
SP - 1322
EP - 1336
JO - American Journal of Cancer Research
JF - American Journal of Cancer Research
IS - 6
ER -