Effects of rhubarb extract on radiation induced lung toxicity via decreasing transforming growth factor-beta-1 and interleukin-6 in lung cancer patients treated with radiotherapy

Department of Radiation Oncology, Qilu Hospital, Medical school, Shandong University, Jinan, Shandong Province 250012, China.
Lung Cancer (Impact Factor: 3.74). 02/2008; 59(2):219-26. DOI: 10.1016/j.lungcan.2007.08.007
Source: PubMed

ABSTRACT Radiation induced lung toxicity (RILT) is the main adverse effect in the radiation therapy of lung cancer. However, the optimal management of RILT has not been defined. In this paper, we investigated the effects of rhubarb extract on RILT, pulmonary function (PF), transforming growth factor-beta-1 (TGF-beta1), and interleukin-6 (IL-6) in lung cancer patients treated with radiotherapy.
We conducted a randomized, double-blind, placebo-controlled trial. Eighty consecutive patients were randomly enrolled into two groups: trial group and control group. The trial group received three-dimensional conformal radiation therapy (3D-CRT) plus rhubarb (at a dose of 20 mg kg(-1) once a day) for 6 weeks. The control group received 3D-CRT plus a placebo containing starch for 6 weeks. Plasma TGF-beta1 and serum IL-6 were measured in all patients before, every 2 weeks during, and at 6 weeks after the completion of the treatment. RILT and PF were evaluated at 6 weeks and 6 months after the end of the treatment, respectively. The differences of TGF-beta1, IL-6, RILT, and PF between the two groups were analysed.
The incidence of RILT in the trial group was significantly lower than that in the control group at 6 weeks and 6 months after treatment (32.4% versus 56.7% at week 6, and 27.0% versus 52.8% at month 6, both P<0.05). The plasma TGF-beta1 levels in the trial group were significantly lower than that in the control group during and after the treatment (P<0.05 or 0.01, respectively). The serum IL-6 levels in the trial group were significantly lower than that in the control group during the treatment (all P<0.01). The forced vital capacity (FVC), forced expiratory volume at 1s (FEV1) at 6 weeks and the diffusion capacity for carbon monoxide (DLCO) at 6 months in the trial group were significantly improved compared to the control group (P<0.05 or 0.01, respectively).
The rhubarb extract significantly attenuated RILT and improved PF, probably by decreasing the level of TGF-beta1 and IL-6. These results may be of value for the prophylaxis of RILT, but the exact mechanisms underlying these prophylactic effects remain to be further explored.

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    • "Total rhubarb anthraquinones (TRAs), active therapeutic components that have been isolated from rhubarb roots (Rheum palmatum L. or Rheum tanguticum Maxim.), have been widely used in traditional Chinese medicine for centuries. Recent studies have demonstrated many pharmacological properties of rhubarb extracts , such as purgative (Peigen et al., 1984; Xu et al., 2011), anti-inflammatory (Cuellar et al., 2001; Gao et al., 2011), liver protection (Zhao et al., 2009), and attenuation of radiation-induced lung toxicity (Yu et al., 2008). Despite its therapeutic value, potential side effects of rhubarb extracts have been shown in experimental studies. "
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    • "The relative contents of rhein and emodin in TRAs (used in our labs) are about 19% and 27%, respectively, and the chemical structures of them are shown in Fig. 1. Recent studies revealed that rhubarb extracts are able to attenuate acute pancreatitis, liver fibrosis and radiation-induced lung toxicity by decreasing the level of transforming growth factor-beta-1 (TGF-␤1)(Yu et al., 2007; Zhan et al., 2000; Zhao et al., 2004). Moreover, experimental studies have suggested that emodin exerts antiproliferative effects in several cancer cell lines through mitochondria (Srinivas et al., 2003), activation of caspase 3 and caspase 9 (Lee, 2001; Srinivas et al., 2003), but independent of reactive oxygen species (ROS) production (Chen et al., 2002). "
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