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Phycocyanin Enhances the Cytotoxic Profile of Cisplatin in Platinum‐Resistant Ovarian Cancer Cells by Targeting Focal Adhesion Kinase
Author(s) -
Levy Arkene,
Joseph Shona,
Hussain Syed,
Saleem Mir,
Rathinavelu Appu
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.816.10
Subject(s) - cisplatin , cancer research , apoptosis , focal adhesion , ovarian cancer , cytotoxic t cell , mtt assay , metastasis , dna fragmentation , cancer cell , cancer , programmed cell death , chemistry , medicine , biology , cell , chemotherapy , in vitro , biochemistry
Platinum‐based therapy is one of the major treatment approaches in ovarian cancer. Although greater than 80% of advanced stage ovarian cancer patients initially achieve remission with platinum therapy; the majority of this cohort eventually relapse, and develop drug‐resistant disease. Resistance to chemotherapeutic drugs such as cisplatin has been attributed in part to the overexpression of Focal Adhesion Kinase (FAK), which is known to promote cancer cell survival and metastasis. In recent years, there has been heightened interest in targeting focal adhesion kinase in platinum resistant cancer as a new modality in ovarian cancer treatment. In previous studies, we have reported that Phycocyanin (C‐PC), a major accessory pigment in the Limnothrix sp. 37‐2‐1, demonstrates cytotoxicity towards multiple cancer cell lines. Therefore, in the present study we evaluated the ability of C‐PC to sensitize platinum resistant OVCAR3 cells to cisplatin treatment. We also examined the response of FAK activation by phosphorylation, to treatment with cisplatin and CP‐C alone, and in combination (C‐PC +cisplatin). Cell viability was determined by MTT assay, and DNA fragmentation was used to confirm apoptotic cell death. The expression of phosphorylated FAK (pFAK), total FAK, pAKT, as well as the key apoptotic regulators p21, p53, Bax, and Bcl‐2 in response to the treatments were determined through western blotting. The results from our study confirm that C‐PC significantly enhances the cytotoxic profile of cisplatin in OVCAR‐3 cells through the induction of apoptosis as confirmed by the presence of DNA fragmentation patterns in all three treatment groups. The expression of activated pFAK was also significantly reduced in the CPC and CPC + cisplatin treatment groups and this corresponded with increased p53, p21 and Bax expression, while pAkt and Bcl‐2 expression was downregulated. These results confirm a novel effect of CPC on FAK phosphorylation in platinum resistant ovarian cancer, which can be further explored towards the treatment of advanced stage disease through combination strategies. Support or Funding Information This project was supported by The Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .