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Nitric Oxide Improves Cisplatin Cytotoxicity in Head and Neck Squamous Cell Carcinoma
Author(s) -
Azizzadeh Babak,
Yip Helena T.,
Blackwell Keith E.,
Horvath Steve,
Calcaterra Thomas C.,
Buga Georgette M.,
Ignarro Louis J.,
Wang Marilene B.
Publication year - 2001
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/00005537-200111000-00004
Subject(s) - cisplatin , cytotoxicity , head and neck squamous cell carcinoma , nitric oxide , cancer research , cell culture , chemistry , cell , in vitro , cytotoxic t cell , medicine , pharmacology , chemotherapy , head and neck cancer , biology , biochemistry , cancer , genetics
Objective To test whether nitric oxide (NO) enhances the cytotoxicity of cisplatin in a head and neck squamous cell carcinoma (HNSCC) cell line. Background Cisplatin is one of the most frequently used chemotherapeutic agents in the treatment of HNSCC. NO has been shown to play an important role in regulating tumor growth. Previous studies demonstrate that NO can enhance the cytotoxicity of cisplatin in Chinese hamster lung fibroblasts. In this report, we examined the in vitro interaction of NO and cisplatin in a HNSCC cell line. Materials and Methods CCL23 cells were pretreated with three different NO donors: PAPA/NO (t 1/2 = 15 min), DPTA/NO (t 1/2 = 3 h), and DETA/NO (t 1/2 = 20 h). The cells were rinsed and exposed for 6 hours to a culture medium containing cisplatin. Cell survival and LD 50 of cisplatin were calculated with and without NO pretreatment. Results PAPA/NO and DPTA/NO did not show any cytotoxic activity and did not change the LD 50 of cisplatin. DETA/NO when used alone resulted in 25.6% cell death at its peak dose (100 μM). Pretreatment with DETA/NO resulted in almost a threefold reduction of the LD 50 of cisplatin (6.8 vs. 2.4 μg/mL). Pretreatment with DETA/NO sensitized the HNSCC cells to subsequent cisplatin activity (two‐sided P = .00016). Conclusion Pretreatment of HNSCC cells with long‐acting NO donors enhances cisplatin activity. Short‐ and medium‐acting NO donors do not exert a toxic effect and do not augment the activity of cisplatin. NO agonists should be considered in the future as a possible adjunct to cisplatin in the treatment of HNSCC. Further studies with animal models are necessary to further clarify this relationship.