Tegillarca granosa extract Haishengsu inhibits the expression of P-glycoprotein and induces apoptosis in drug-resistant K562/ADM cells.
This study was designed to investigate the effect and molecular mechanisms of Haishengsu (HSS), a protein extract from a shellfish Tegillarca granosaL., on a drug resistant leukemia cell line. Cultured K562/Adriamycin (ADM) cells were treated with HSS at 10, 20 and 40 microg/mL, respectively. The apoptosis and expression of p-glycoprotein was evaluated by flow cytometry. Expressions of caspase-3 and Bcl-2 were also evaluated. There was a significant dose-dependent increase in the apoptosis in the HSS treated K562/ADM cells (P < 0.05 and 0.01, respectively). The p-glycoprotein expression in the 40 microg/mL HSS group (14.8%) was lower than in the control (16.9%, P < 0.05) and the 10 microg/mL HSS group (7.3%, P < 0.05), but it was similar to the HSS 20 microg/mL group (10.7%, P > 0.05). The expressions of apoptosis-stimulating protein caspase-3 protein were increased, whereas the expressions of apoptosis-suppressing Bcl-2 were decreased in the HSS groups, as compared with the levels in the control group (P < 0.05). We conclude that HSS induces apoptosis of the Adriamycin-resistant K562/ADM cells. The enhanced expressions in caspase-3 and the reduced expressions in Bcl-2 protein may have contributed to the apoptosis-stimulating effect of HSS. The inhibition of p-glycoprotein suggests that HSS may diminish the resistance to Adriamycin and potentially enhance the therapeutic effects.
Li
Guang-Yao
GY
Liaocheng People's Hospital (Liaocheng Clinical School of Taishan Medical University), Liaocheng Shandong, 252000, PR China.
Liu
Ji-Zhu
JZ
Chen
Shou-Guo
SG
Zhang
Bin
B
Wang
Chun-Bo
CB
Wang
Le-Xin
LX
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000418:Albumins / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D010865:Pilot Projects; D012758:Shellfish
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000418:Albumins; D004365:Drugs, Chinese Herbal; C532636:haishengsu; D004317:Doxorubicin