Background:

Camptothecin is a selective inhibitor of topoisomerase I with IC50 value of 679 nM [1].

Camptothecin could induce cell death in SMMC-7721, MCF-7, and HCT-116 tumor cells. Camptothecin has been reported to induce autophagy via AMPK-TSC2-mTOR pathway, at the mean time, induce premature senescence?by ATM-Chk2-p53-p21?pathway [2].

Studies indicated that camptothecin had anti-tumor activity in (non-small cell lung cancer) NSCLC xenografts. Camptothecin -induced DNA damage has revealed to cause phosphorylation of H2AX (γH2AX).?Previous studies have also demonstrated to reduce the expression of Top1 in cancer cells treated with camptothecins [3].

参考文献:
[1] Luzzio MJ1,?Besterman JM,?Emerson DL,?Evans MG,?Lackey K,?Leitner PL,?McIntyre G,?Morton B,?Myers PL,?Peel M, et al. Synthesis and antitumor activity of novel water soluble derivatives of camptothecin as specific inhibitors of topoisomerase I. J Med Chem.?1995 Feb 3;38(3):395-401.
[2] Zhang JW1,?Zhang SS1,?Song JR2,?Sun K3,?Zong C1,?Zhao QD1,?Liu WT1,?Li R1,?Wu MC1,?Wei LX4. Autophagy inhibition switches low-dose camptothecin-induced premature senescence to apoptosis in human colorectal cancer cells. Biochem Pharmacol.?2014 May 22. pii: S0006-2952(14)00286-X.
[3] Tsakalozou E1,?Adane ED,?Liang Y,?Arnold SM,?Leggas M. Protracted dosing of the lipophilic camptothecin analogue AR-67 in non-small cell lung cancer xenografts and humans. Cancer Chemother Pharmacol.?2014 May 8. [Epub ahead of print]