8-Chloroadenosine

8-Chloroadenosine (8-Cl-Ado), a unique ribonucleoside analog, depletes endogenous ATP that subsequently induces the phosphorylation and activation of AMPK. 8-Chloroadenosine induces autophagic cell death. 8-Chloroadenosine effectively inhibited in vivo tumor growth in mice[1].

Signaling Pathways >> Epigenetics >> AMPK

Research Areas >> Cancer

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> PI3K/Akt/mTOR >> AMPK

AMPK

8-Chloroadenosine (8-Cl-Ado; 10 μM; 24-72 hours) induces an autophagic flux in both LC3B-II and p62 levels[1]. 8-Chloroadenosine (10 μM; 7-21 hours) induces phosphorylation of AMPK (Thr172) in a time-dependent manner in MCF-7 and BT-474 cells. Total AMPK protein levels were unchanged. 8-Chloroadenosine readily induces the phosphorylation of raptor Ser792 in MCF-7 cells. 8-Chloroadenosine (10 μM; 4-72 hours) induces ULK1 phosphorylation on Ser555 in MCF-7 and BT-474 cells[1]. 8-Chloroadenosine attenuates mTOR activity in breast cancer cells. 8-Chloroadenosine is independent of p53[1]. 8-Chloroadenosine (10 μM; 3 days) inhibits over 90% clonogenic survival in the MCF-7 breast cancer cell lines. The amount of apoptosis induction only reached ~30%[1]. 8-Chloroadenosine (10 μM) treatment results in a rapid depletion of ATP within 12-hours in T47D, SK-BR-3, and ZR-75-1 cells[1].

8-Chloroadenosine (25-100 mg/kg; IP; three times a week for 3 weeks) inhibits growth of both MCF-7 and BT-474 xenograft tumors with 100 mg/kg. 8-Chloroadenosine with 50 mg/kg dose does not affect the growth of the BT-474 xenograft tumors[1].

[1]. Christine M Stellrecht, et al. ATP directed agent, 8-chloro-adenosine, induces AMP activated protein kinase activity, leading to autophagic cell death in breast cancer cells. J Hematol Oncol. 2014 Mar 14;7:23.