Benzyl isothiocyanate sensitizes human pancreatic cancer cells to radiation therapy.

نویسندگان

  • Ravi Prakash Sahu
  • Michael Wayne Epperly
  • Sanjay Kumar Srivastava
چکیده

Increase in systemic toxicity and resistance are the major drawbacks of radiation therapy in the treatment of pancreatic cancer. We have shown previously that BITC inhibits the growth of human pancreatic cancer cells and induces apoptosis. Here we determined whether BITC could sensitize BxPC-3 cells and increase the therapeutic potential of gamma-irradiation. Cells were pretreated with 2.5 microM BITC for 24h followed by exposure to 5 Gy of gamma-irradiation and were allowed to grow for another 24 or 48 h before being analyzed. Combination of BITC and gamma-irradiation significantly reduced survival of cells and caused significantly enhanced arrest of cells in G2/M phase as compared to cells exposed to gamma-irradiation alone. G2/M arrest was associated with DNA damage leading to the phosphorylation of ATR (Ser-428), Chk2 (Thr-68), Cdc25C (Ser-216), Cdk-1 (Tyr-15) and induction of p21Waf1/Cip1. However, combination treatment after 48 h caused 2.8-fold increase in apoptosis in BxPC-3 cells. Apoptosis at 48 h was associated with NF-kappa B inhibition and p38 activation. Taken together, results of the present study suggest that the apoptosis-inducing effect of gamma-irradiation can be increased by BITC.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Anti-proliferative and proapoptotic effects of benzyl isothiocyanate on human pancreatic cancer cells is linked to death receptor activation and RasGAP/Rac1 down-modulation.

Benzyl isothiocyanate can exert anti-tumor effect by arrest of cell cycle progression and induction of apoptosis in human pancreatic cancer cells. Among them, the dissection of the molecular mechanism of induction of apoptosis is important because the knowledge may be exploited for both cancer prevention and treatment. Our studies reported here indicate that BITC-mediated apoptosis involves the...

متن کامل

The role of STAT-3 in the induction of apoptosis in pancreatic cancer cells by benzyl isothiocyanate.

BACKGROUND Benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables, has been reported to have anticancer properties, but the mechanism whereby it inhibits growth of human pancreatic cancer cells is incompletely understood. METHODS Human pancreatic cancer cells (BxPC-3, AsPC-1, Capan-2, MiaPaCa-2, and Panc-1) and immortalized human pancreatic cells (HPDE-6) were treated with v...

متن کامل

Atorvastatin Sensitizes Breast and Lung Cancer Cells to Ionizing Radiation

Tumour cells may be resistant to radiotherapy that results in unsuccessful cancer treatment in patients. The aim of this study was to evaluate the sensitizing effect of atorvastatin (ATV) on breast cancer (MDA-MB-231) and non-small cell lung cancer (A-549) cells following exposure to ionizing radiation (IR). These cells were treated with ATV and exposed to X-ray at dose 4 Gy. The radiosensitizi...

متن کامل

Atorvastatin Sensitizes Breast and Lung Cancer Cells to Ionizing Radiation

Tumour cells may be resistant to radiotherapy that results in unsuccessful cancer treatment in patients. The aim of this study was to evaluate the sensitizing effect of atorvastatin (ATV) on breast cancer (MDA-MB-231) and non-small cell lung cancer (A-549) cells following exposure to ionizing radiation (IR). These cells were treated with ATV and exposed to X-ray at dose 4 Gy. The radiosensitizi...

متن کامل

Cell cycle arrest, apoptosis induction and inhibition of nuclear factor kappa B activation in anti-proliferative activity of benzyl isothiocyanate against human pancreatic cancer cells.

Benzyl isothiocyanate (BITC), a cruciferous vegetable-derived compound, has been shown to inhibit chemically induced cancer in animal models. Moreover, epidemiological studies have provided compelling evidence to suggest that cruciferous vegetables may be protective against cancer risk. Here, we report that BITC significantly inhibits growth of human pancreatic cancer BxPC-3 cells in a concentr...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Frontiers in bioscience

دوره 1  شماره 

صفحات  -

تاریخ انتشار 2009