Curcumin inhibits carcinogen and nicotine-induced mammalian target of rapamycin pathway activation in head and neck squamous cell carcinoma

Cancer Prev Res. 2010;3(12):1586-95

 

Despite of decrease in the prevalence of cigarette smoking, in the USA, 30% of cancer deaths are due to cigarette smoking and 90-95% of diagnosed head and neck squamous cell carcinoma (HNSCC) are tobacco-related with ~40,000 new cases, 13,000 U.S. deaths and 500,000 new cases worldwide. It has been found that cigarette smokers are 3 times more likely to develop smoking-related second primary tumors than non-smokers. Hence, there is urgent need for chemopreventive agents.

Tobacco use at HNSCC diagnosis is a recognized risk factor for second primary tumors (SPTs), and current smokers are 3 times more likely than never-smokers to develop smoking-related SPT (6), indicating a need for chemopreventive agents among tobacco users.

One promising agent is Curcumin, which has been implicated as a powerful therapeutic agent in several human cancers, as it has the ability to block tumor initiation and progression in several types of cancers.

 

Objective:

To examine the effects of Curcumin on HNSCC growth in a variety of HNSCC cell lines, xenograft model and in a carcinogen-induced survival study.

 

Study Design:

  • Three HNSCC cell lines, FaDu, SCC25 and OKF6 were evaluated for influence of Curcumin on cell proliferation and cell motility
  • In the xenograft model, Balb/c nu/nu mice (4-6 weeks old) were injected SCC40 cells
  • Once tumors reached 40 mm3, treatment was initiated with Curcumin (0, 5, 10 or 15 mg) (considered as day 0)
  • Similarly, 10 Balb/c nu/nu mice per group were pretreated for 4 days with Curcumin (0, 10 or 15 mg) and injected with SCC40 cells, to determine the chemopreventive effects of Curcumin prior to grafting
  • Mice continued to receive curcumin for the remainder of the study and the control group received vehicle only
  • Tumor volumes were compared on day 24, the last day when all control mice were still alive
  • In oral carcinogen-induced model, 24 CBA/CaJ mice (4-6 weeks old) were painted in their oral cavity with 5 mg/mL (3 times per week) tobacco-derivative 4-nitroquinoline 1-oxide (4NQO), to mimic tobacco-induced carcinogenesis in humans for 20 weeks and followed up to 50 weeks
  • Simultaneously, mice were also painted with 0, 5, 10 or 15 mg Curcumin (5 times per week) to determine its anticarcinogenic activity

 

Results and Discussion:

  • Cell proliferation assay demonstrated that HNSCC cells were more sensitive to Curcumin compared to normal cells after 72 h
  • In xenograft model, a significant reduction in tumor volume was observed with 15 mg of Curcumin at day 5 and day 8, compared to control
  • In oral carcinogen-induced model, Curcumin inhibited oral tumor growth compared with control with no visible tumors formed in the highest curcumin dose (15 mg) group
  • Curcumin inhibited gene products modulated by the mTOR pathway induced by nicotine both in vitro and in vivo

 

Conclusion:

Curcumin effectively inhibited the adverse effects of nicotine by blocking nicotine-induced activation of the AKT/MTOR pathway in HNSCC, in turn retarding cell migration, suggesting that Curcumin may be useful as an oral chemopreventive agent.

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Sabinsa Corporation is a manufacturer, supplier and marketer of herbal extracts, cosmeceuticals, minerals, dietary supplements and specialty fine chemicals for the nutritional, cosmetic, pharmaceutical and food industries.

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