Acetyl-11-keto-ß-boswellic acid triggers premature senescence via induction of DNA damage accompanied by impairment of DNA repair genes in hepatocellular carcinoma cells in vitro and in vivo.

Cellular senescence, a state of irreversible growth arrest, occurs in all somatic cells and causes the cells to exhaust replicative capacity. Recently, cellular senescence has been emerging as one of the principal mechanisms of tumor suppression, which can be induced by low doses of therapeutic drugs in cancer cells. Acetyl-11-keto-ß-boswellic acid (AKBA), an active ingredient isolated from the plant Boswellia serrata, has been identified to induce apoptosis in hepatocellular carcinoma (HCC) cells. In this study, we found that low concentrations of AKBA treatment triggered cell growth arrest at G0/G1 phase with features of premature cellular senescence phenotype in both HCC cell lines HepG2 and SMMC7721, as observed by enlarged and flattened morphology, significant increase in cells with senescence-associated ß-galactosidase staining, and decrease in cell proliferation and DNA synthesis. Furthermore, cellular senescence induced by AKBA occurred via activation of DNA damage response and impairment of DNA repair, as evidenced by strong induction of γH2AX and p53, and downregulated expressions of multiple DNA repair associated genes. Induction of p53 by AKBA caused a significant increase in p21CIP1 , which had a critical involvement in the induction of cellular senescence. Additionally, in vivo study demonstrated that induction of senescence contributed to the anticancer efficacy of AKBA. Therefore, our findings suggested that induction of premature senescence by AKBA through DNA damage response accompanied by impairment of DNA repair genes defines a novel mechanism contributing to its growth suppression in HCC cells.

[A long-term follow-up of lumbar laminotomy and replantation].

OBJECTIVE: To evaluate lumbar laminotomy and replantation in prevention of spinal unstability and peridural adhesion after laminectomy. METHODS: From February 1995 to March 2001, a total of 169 patients (96 males, 73 females, aged 22-63) with lesions in the lumbar vertebral canals underwent surgery, in which the lesions were removed after laminectomy and then the excised laminae were replanted. RESULTS: The follow-up for 5-9 years showed that all the patients had no complications after the lesions were removed. According to the evaluation criteria formulated by WANG Yongti, 81 patients had an excellent result, 67 had a good result, 19 had a fair result, and 2 had a poor result. 87.6% of the patients obtained quite satisfactory results. The X-ray films demonstrated that the replanted laminae obtained bony healing and the spine was stable. The CT scanning demonstrated that the canals were enlarged with a smooth and glossy interior. CONCLUSION: Lumbar laminotomy and replantation is reasonable in design and convenient in performance, which can be promoted as a basic operation in spinal surgery.