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Cellular senescence is a key physiological barrier against tumor and represents an option for therapeutic intervention. One pivotal intracellular stimulus causing senescence is DNA damage response, while the senescence-associated heterochromatin in cancer limits the strength of the DNA damage response to endogenous genotoxic stress or DNA-damaging agents. Therefore, targeting the maintenance of compacted chromatin in cancer cells represents an optional intervention to improve the therapeutic efficacy in cancer treatment. Given a crosstalk between methionine cycle and histone methylation, we hypothesize that pharmacologically disrupting methylation potential, defined as the ratio of cellular S-adenosylmethionine to S-adenosylhomocysteine, could affect the chromatin structures in cancer cells and thus enhance their sensitivity to DNA damage response signaling. Our results showed that 3-deazaneplanocin A, a chemical inhibitor of S-adenosylhomocysteine hydrolase, elicited a typical cellular senescence in hepatoma cells. Therapy-induced senescence by 3-deazaneplanocin A was mediated through p53–p21 pathway and triggered by enhanced ataxia-telangiectasia mutated activation related to chromatin changes. In conclusion, our study demonstrated that metabolic perturbation of chromatin status in oncogene-activated cancers could be an optional intervention to sensitize DNA damage response signaling.

Cytokine-induced killer (CIK) cell immunotherapy exhibits significant advantages in the clinical treatment of tumors. This study was designed to compare the biological characteristics of autologous CIK cells from patients with hepatocarcinoma following different procedures for the separation of peripheral blood mononuclear cells (PBMCs). Forty-four hepatocarcinoma patients were enrolled and distributed into two groups. PBMCs were isolated either using a blood cell separator (apheresis method) or Ficoll lymphocyte separation medium (Ficoll method). The total amount, collection efficacy, and cell status of PBMCs in the two groups were determined. According to the number and status of collected PBMCs, different cultivation procedures were used for their amplification and activation and the proliferation ability, phenotype, and killing activity of CIK cells in the two groups were evaluated. Our results indicated that the number of collected PBMCs in the apheresis group was far more than that in the Ficoll group. However, the isolation rate was lower, and more cellular debris was observed in the apheresis group, which may be the cause of some untoward effects. Following in vitro culture, the enrichment time of CIK cells was longer in the Ficoll group, and the percentages of CD3(+)CD4(+) (Th) and CD4(+)CD25(+) (Treg) cells were higher. In the apheresis group, the percentages of CD3(-)CD56(+) (NK) and CD3(+)CD56(+) (NKT) cells were higher, and the CIK cells exhibited a higher cytolytic activity against HepG2 hepatoma cells. In conclusion, different procedures for PBMCs separation can influence the biological activities of CIK cells, and the apheresis method is more effective at enhancing the antitumor efficacy of CIK cells. However, significant attention should be paid to the possibility of adverse reactions in apheresis donors.