The Chinese herb isolate YHL-14 induces G2/M arrest in human cancer cells by up-regulating p21 expression through P53-independent cascade [Signal Transduction]

January 22nd, 2014 by Zhang, R., Wang, Y., Li, J., Jin, H., Song, S., Huang, C.

Yuanhuacine (YHL-14), the major component of daphnane diterpene ester isolated from the flower buds of Daphne genkwa, was reported to have activity against cell proliferation in various cancer cell lines. Nevertheless, the potential mechanism has not been explored yet. Here we demonstrated that YHL-14 inhibited bladder and colon cancer cell growth through up-regulation of p21 expression in p53-independent manner. We found that YHL-14 treatment resulted in up-regulation of p21 and a significant G2/M phase arrest in T24T and HCT116 cells with no effect on p53 protein expression. Further studies indicated that p21 induction by YHL-14 was regulated at the transcription level via up-regulation of Sp1 protein expression. Moreover, our results showed that p38 played an essential role in YHL-14-mediated Sp1 protein stabilization, G2/M growth arrest induction and anchorage-independent growth inhibition of cancer cells. Taken together, our studies demonstrate a novel mechanism of YHL-14 against cancer cell growth in bladder and colon cancer cell lines, which provides valuable information for designing and synthesis of other new conformation-constrained derivatives based on the structure of YHL-14 for the cancer therapy.
  • Posted in Journal of Biological Chemistry, Publications
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