Cytotoxicity of calotropin is through caspase activation and downregulation of anti-apoptotic proteins in K562 cells.
Calotropin is one of cardenolides isolated from milkweed used for medicinal purposes in many Asian countries. Whereas calotropin possesses cytotoxicity against several cancer cells, the mechanisms of action remain unclear. We set out to evaluate the cytotoxic mechanism of calotropin on human chronic myeloid leukemia K562 cells. Calotropin inhibited the growth of K562 cells in a time- and dose-dependent manner by G(2)/M phase arrest. It upregulated the expression of p27 leading to this arrest by downregulating the G2/M regulatory proteins, cyclins A and B, and by upregulating the cdk inhibitor, p27. Furthermore, it downregulated anti-apoptotic signaling (XIAP and survivin) and survival pathways (p-Akt and NFkappaB), leading to caspase-3 activation which resulted in the induction of apoptosis. In all, calotropin exerted its anticancer activity on K562 cells by modulating the pro-survival signaling that leads to induction of apoptosis.
Wang
Shih-Chung
SC
Department of Pediatrics, Changhua Christian Hospital, Changhua 500, Taiwan.
Lu
Mei-Chin
MC
Chen
Hsiu-Lin
HL
Tseng
Hsing-I
HI
Ke
Yu-Yuan
YY
Wu
Yang-Chang
YC
Yang
Pei-Yu
PY
D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D031108:Asclepias; D002298:Cardenolides / Q000302:isolation & purification / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells
D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D002298:Cardenolides; C546414:calotropin; D020169:Caspases