Quansheng Zhou, Mengli Zhang and Zhifei Cao
Soochow University, Peoples Republic of China
Posters & Accepted Abstracts: J Cancer Sci Ther
Lung cancer is a leading lethal disease with the 5-year survival rate of the cancer patients only 16%. Inadequate potent anti-lung cancer drugs, particularly for suppression of lung cancer stem cells, appear to be a bottleneck in the treatment of the disease; hence, the effective anti-lung cancer drug is highly desired. In this study, we aim to explore new compound against lung cancer. Using human H1299 and A549 lung carcinoma cell lines as a model to screen and test the anti-lung cancerous compounds, we found that triptonide, a bioactive small molecule purified from the herb Tripterygium wilfordii Hook caused a marked suppression of cell proliferation and colony formation of lung cancer cells at very low concentrations of 5-10nM. More interestingly, triptonide robustly inhibited the lung cancer cell formation of tumorspheres, and reduced the stemness and tumorigenicity of the sphereforming cells, suggesting that triptonide is a new inhibitor of cancer stem-like cells. In vivo tumor xenograft assay in mice showed that administration of triptonide at the dose of 5mg/Kg markedly inhibited the tumor growth with low toxicity. Molecular mechanistic studies revealed that triptonide significantly decreased expression of the glioma-associated oncogene 1 (Gli1) at both mRNA and protein levels through repressing Gli1 gene promoter activity. Additionally, triptonide reduced the levels of cancer stem cell key signaling protein sonic hedgehog (Shh), but increased the amount of Ptch1 which is a protein binding to the smoothened protein (SMO) to diminish the Shh signal transduction, resulting in inhibiting an Shh-Gli1 signaling pathway in lung cancer cells. Together, our findings show that triptonide effectively inhibits lung cancer stem-like cell growth, stemness, and tumorigenicity, and support the notion that triptonide is a new inhibitor of cancer stem-like cells and Shh-Gli1 signaling inhibitor, and is a novel anti-lung cancer drug candidate for further developing effective lung cancer therapeutics.
E-mail: [email protected]
Cancer Science & Therapy received 3358 citations as per Google Scholar report