Anti-Lung Cancer Activity through Enhancement of Immunomodulation and Induction of Cell Apoptosis of Total Triterpenes Extracted from Ganoderma luncidum (Leyss. ex Fr.) Karst.

Liang Feng,Meng Du,Jun-Fei Gu,Yan Chen,Wei Cao,Ming-Hua Zhang,Ling Yuan,Ying Wang,Jun-Jie He

doi:10.3390/molecules18089966

Abstract

Ganoderma luncidum (Leyss. ex Fr.) Karst. (GLK) has been used traditionally for the prevention and treatment of cancers or tumors for a long time in Traditional Chinese Medicine. The triterpenes as main effective components of GLK have been found to be beneficial for the efficacy. The purpose of this study was to examine the anti-lung cancer activity of triterpenes of GLK in vitro and in vivo and to explore their anti-lung cancer effects and potential mechanisms. A549 cells and Lewis tumor-bearing mice were used to evaluate the inhibition effects of triterpenes on cell proliferation and tumor growth. The IC50 of triterpenes of GLK on A549 cells was 24.63 μg/mL. Triterpenes of GLK could significantly inhibit tumor growth in mice (30, 60 and 120 mg/kg). The immune organs indexes including spleen and thymus were increased remarkedly by the treatment with triterpenes. Moreover, they were able to stimulate the immune response by increasing the expressions of IL-6 and TNF-α. Flow cytometric analysis revealed that cell arrest caused by triterpenes treatment (7.5, 15 and 30 μg/mL) was in the G2/M phase in A549 cells. Triterpenes induced apoptosis by decreasing the expression of the antiapoptotic protein Bcl-2 and pro-caspase 9 and increasing the levels of cleaved-caspase 9. Our findings suggested that the triterpenes of GLK have anti-lung cancer activity in vitro and in vivo via enhancement of immunomodulation and induction of cell apoptosis. The study provides insights into the mechanism of GLK in the prevention and treatment of lung cancer.

Highlights

Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer death worldwide [1]
The chromatogram showed that triterpenes of GLK could be eluted completely under the HPLC conditions used within 128 min, and separated satisfactorily
There is a decrease at 30 μg/mL concentration. This might be related to the transformation of early apoptosis to late apoptosis. These findings indicated that the triterpenes of GLK could induce A549 cell apoptosis to inhibit tumor growth in A549 cells

Summary

Introduction

Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer death worldwide [1]. Some current treatments involving non-selective cytotoxic chemotherapy, radiotherapy and surgery may result in only a modest increase in survival and a significant toxicity for the patient with lung cancer [2]. Traditional Chinese Medicine has been found to be beneficial for the prevention and treatment of cancers/tumors through mutiple mechanisms, including immunostimulation and the induction of apoptosis [3]. The combined effects of the multi-component medicines may contribute to the inhibition of tumor growth. They can enhance the body’s immunity with low side effects and toxicity [4,5].

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