FK-16 Derived from the Anticancer Peptide LL-37 Induces Caspase-Independent Apoptosis and Autophagic Cell Death in Colon Cancer Cells
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AbstractHost immune peptides, including cathelicidins, have been reported to possess anticancer properties. We previously reported that LL-37, the only cathelicidin in humans, suppresses the development of colon cancer. In this study, the potential anticancer effect of FK-16, a fragment of LL-37 corresponding to residues 17 to 32, on cultured colon cancer cells was evaluated. FK-16 induced a unique pattern of cell death, marked by concurrent activation of caspase-independent apoptosis and autophagy. The former was mediated by the nuclear translocation of AIF and EndoG whereas the latter was characterized by enhanced expression of LC3-I/II, Atg5 and Atg7 and increased formation of LC3-positive autophagosomes. Knockdown of Atg5 or Atg7 attenuated the cytotoxicity of FK-16, indicating FK-16-induced autophagy was pro-death in nature. Mechanistically, FK-16 activated nuclear p53 to upregulate Bax and downregulate Bcl-2. Knockdown of p53, genetic ablation of Bax, or overexpression of Bcl-2 reversed FK-16-induced apoptosis and autophagy. Importantly, abolition of AIF/EndoG-dependent apoptosis enhanced FK-16-induced autophagy while abolition of autophagy augmented FK-16-induced AIF-/EndoG-dependent apoptosis. Collectively, FK-16 induces caspase-independent apoptosis and autophagy through the common p53-Bcl-2/Bax cascade in colon cancer cells. Our study also uncovered previously unknown reciprocal regulation between these two cell death pathways. © 2013 Ren et al.
All Author(s) ListRen S.X., Shen J., Cheng A.S.L., Lu L., Chan R.L.Y., Li Z.J., Wang X.J., Wong C.C.M., Zhang L., Ng S.S.M., Chan F.L., Chan F.K.L., Yu J., Sung J.J.Y., Wu W.K.K., Cho C.H.
Journal namePLoS ONE
Detailed descriptionTo ORKTS: Through Ms Jelly Cheung, clarified by Jing Shen, this is a typo on the paper that "Jin Shen" should be "Jing Shen", who is currently a Resea
Year2013
Month5
Day20
Volume Number8
Issue Number5
PublisherPublic Library of Science
Place of PublicationUnited States
ISSN1932-6203
LanguagesEnglish-United Kingdom

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