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A new gamboge derivative compound 2 inhibits cancer stem-like cells via suppressing EGFR tyrosine phosphorylation in head and neck squamous cell carcinoma.

Deng R, Wang X, Liu Y, Yan M, Hanada S, Xu Q, Zhang J, Han Z, Chen W, Zhang P - J. Cell. Mol. Med. (2013)

Bottom Line: Interestingly, when compared with cisplatin (CDDP), C2 effectively suppresses the growth of both cancer stem-like cells and non-cancer stem-like cells derived from head and neck squamous cell carcinoma (HNSCC), inhibiting the formation of tumour spheres and colony in vitro, resulting in the loss of expression of multiple cancer stem cell (CSC)-related molecules in HNSCC.Treating with C2 effectively inhibited the growth of HNSCC in BALB/C nude mice.Further investigation found that C2 notably inhibits the activation of epithelial growth factor receptor and the phosphorylation of its downstream protein kinase homo sapiens v-akt murine thymoma viral oncogene homolog (AKT) in HNSCC, resulting in down-regulation of multiple CSC-related molecules in HNSCC.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China; Department of Oral and Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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Inhibitory effects of C2 on head and neck squamous cell carcinoma (HNSCC) cells. (A) The 50% inhibitory concentration (IC50) of C2 and CDDP on different HNSCCs. (B) The inhibitory effects of C2 on normal cells (from left to right: periodontal cells, umbilical vein endothelial cells and oral mucosa cells).
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fig01: Inhibitory effects of C2 on head and neck squamous cell carcinoma (HNSCC) cells. (A) The 50% inhibitory concentration (IC50) of C2 and CDDP on different HNSCCs. (B) The inhibitory effects of C2 on normal cells (from left to right: periodontal cells, umbilical vein endothelial cells and oral mucosa cells).

Mentions: To study the effect of C2 on cancer cells, we first examined the viability of seven cancer cells treated with gradient dosages of C2 for 72 hrs with MTT assay. As shown in Figure 1A, the inhibitory efficacy of C2 on cancer cells was more successful compared with the traditional chemotherapeutic drug CDDP. The IC50 of C2 on different cancer cells was from 0.144 μM (HN4) to 0.885 μM (HN13), with median value 0.59 μM, while the IC50 of CDDP was from 3.065 μM (Cal 27) to 4.881 μM (KB/VCR), with median value 3.839 μM (Table S1). Some cancer cells showed less sensitive to C2, while others were more sensitive, indicating selective effects of C2 on different cells, while the IC50 of CDDP was more consistent across all cancer cell lines. We also examined the toxicity of C2 on various primary cultured normal cells, including periodontal cells, umbilical vein endothelial cells, and oral mucosa cells. As Figure 1B shows, the IC50 of C2 on normal cells was from 1.212 to 3.345 μM, with median 1.98 μM, which was about three times higher than the IC50 of C2 on cancer cells.


A new gamboge derivative compound 2 inhibits cancer stem-like cells via suppressing EGFR tyrosine phosphorylation in head and neck squamous cell carcinoma.

Deng R, Wang X, Liu Y, Yan M, Hanada S, Xu Q, Zhang J, Han Z, Chen W, Zhang P - J. Cell. Mol. Med. (2013)

Inhibitory effects of C2 on head and neck squamous cell carcinoma (HNSCC) cells. (A) The 50% inhibitory concentration (IC50) of C2 and CDDP on different HNSCCs. (B) The inhibitory effects of C2 on normal cells (from left to right: periodontal cells, umbilical vein endothelial cells and oral mucosa cells).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4117555&req=5

fig01: Inhibitory effects of C2 on head and neck squamous cell carcinoma (HNSCC) cells. (A) The 50% inhibitory concentration (IC50) of C2 and CDDP on different HNSCCs. (B) The inhibitory effects of C2 on normal cells (from left to right: periodontal cells, umbilical vein endothelial cells and oral mucosa cells).
Mentions: To study the effect of C2 on cancer cells, we first examined the viability of seven cancer cells treated with gradient dosages of C2 for 72 hrs with MTT assay. As shown in Figure 1A, the inhibitory efficacy of C2 on cancer cells was more successful compared with the traditional chemotherapeutic drug CDDP. The IC50 of C2 on different cancer cells was from 0.144 μM (HN4) to 0.885 μM (HN13), with median value 0.59 μM, while the IC50 of CDDP was from 3.065 μM (Cal 27) to 4.881 μM (KB/VCR), with median value 3.839 μM (Table S1). Some cancer cells showed less sensitive to C2, while others were more sensitive, indicating selective effects of C2 on different cells, while the IC50 of CDDP was more consistent across all cancer cell lines. We also examined the toxicity of C2 on various primary cultured normal cells, including periodontal cells, umbilical vein endothelial cells, and oral mucosa cells. As Figure 1B shows, the IC50 of C2 on normal cells was from 1.212 to 3.345 μM, with median 1.98 μM, which was about three times higher than the IC50 of C2 on cancer cells.

Bottom Line: Interestingly, when compared with cisplatin (CDDP), C2 effectively suppresses the growth of both cancer stem-like cells and non-cancer stem-like cells derived from head and neck squamous cell carcinoma (HNSCC), inhibiting the formation of tumour spheres and colony in vitro, resulting in the loss of expression of multiple cancer stem cell (CSC)-related molecules in HNSCC.Treating with C2 effectively inhibited the growth of HNSCC in BALB/C nude mice.Further investigation found that C2 notably inhibits the activation of epithelial growth factor receptor and the phosphorylation of its downstream protein kinase homo sapiens v-akt murine thymoma viral oncogene homolog (AKT) in HNSCC, resulting in down-regulation of multiple CSC-related molecules in HNSCC.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China; Department of Oral and Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Show MeSH
Related in: MedlinePlus