Effect of ginseng saponin, arsenic trioxide, beta-elemene combined with CTX on telomere-telomerase system in K562 cell line.
This study was aimed to investigate the modulating effects on telomere length and telomerase activity in K562 cells treated by arsenic trioxide, ginseng saponin, beta-elemene alone or in combination with cyclophosphamide (CTX) and to explore the possible mechanism and new therapy for acute leukemia. Human erythroleukemic cell line K562 was co-cultured with the above-mentioned drugs. Cells were collected after 24, 48 and 72 hours for further detection. Telomere length and telomerase activity were detected by Southern-blot and PCR-ELISA respectively. The effects of these drugs were observed at different concentrations and exposure time. The results showed that (1) ginseng saponin, arsenic trioxide, beta-elemene, or CTX could completely inhibit the telomerase activity of K562 cells at proper concentrations and exposure time. The inhibiting effects were enhanced when the three former drugs were used with CTX. Telomerase activity decreased proportionally with the concentrations and length of time. (2) viability of K562 cells was decreased after being co-cultured with arsenic trioxide, ginseng saponin, beta-elemene and CTX. The level of inhibition depends on the concentration and exposure time. (3) telomere length of K562 cells was 5.36 +/- 0.18 kb. After being co-cultured with those drugs for 72 hours, telomere length was 5.90 kb -6.50 kb, significantly longer than that of control (5.18 - 5.35 kb). It is concluded that arsenic trioxide, ginseng saponin, and beta-elemene can inhibit the growth and telomerase activity of K562 cells. The inhibiting effects were enhanced when they were used in combination with CTX. The depression of telomerase activity may be one of the mechanisms of anti-tumor effect. Less dosage and shorter course can be expected when arsenic trioxide, ginseng saponin, and beta-elemene are used in combination with CTX. When telomerase activity was depressed, the telomere length prolonged a little, indicating K562 cell line may extend telomeres by some alternative way other than telomerase activation.
Wang
Yi
Y
Department of Hematology, The First Affiliated Hospital, Dalian Medical University, Dalian 116011, China.
Fang
Mei-Yun
MY
D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D020014:K562 Cells; D010087:Oxides / Q000494:pharmacology*; D005894:Panax / Q000737:chemistry; D012503:Saponins / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000494:pharmacology*; D019098:Telomerase / Q000187:drug effects* / Q000378:metabolism; D016615:Telomere / Q000187:drug effects
D001152:Arsenicals; D010087:Oxides; D012503:Saponins; D012717:Sesquiterpenes; C445979:beta-elemene; D003520:Cyclophosphamide; D019098:Telomerase; D000077237:Arsenic Trioxide