title: ALLN hinders HCT116 tumor growth through Bax-dependent apoptosis.
abstract: Continual high expression of cysteine proteases calpain I and II have been implicated in tumorigenicity; conversely, N-acetyl-leu-leunorleucinal (ALLN), which inhibits calpain I and II, should also influence tumor growth and carcinogenesis. To explore the role of ALLN against colon cancer and in promoting apoptosis, we used colon cancer HCT116 cell lines, p53 or Bax-deficient HCT116 cell lines. Cell viability and tumor growth decreased in a concentration-dependent manner when treated with 0-26μM ALLN. Treatment with ALLN induced apoptosis in HCT116 cell; however, flow cytometry showed that apoptosis significantly decreased in Bax-deficient HCT116 cell lines, but not in p53-deficient HCT116 cell lines. In addition, the ALLN-induced apoptosis response was through Bax translocation from cytosol to mitochondria. In this study we showed intraperitoneally injected ALLN to inhibit colon tumor formation in nude mice, and found ALLN to inhibit tumor growth in colon cancer cells, mainly through apoptosis that depends on translocation of Bax to a mitochondrial endogenous pathway; this implies a molecular mechanism for ALLN against human colon cancer. These results suggest that ALLN could become a novel agent for prevention of colon cancer.
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Shang-ze
authors.initials: SZ
authors.lastname: Li
authors.forename: Hui-hui
authors.initials: HH
authors.lastname: Zhang
authors.forename: Jia-nong
authors.initials: JN
authors.lastname: Zhang
authors.forename: Ze-yan
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Xiao-fei
authors.initials: XF
authors.lastname: Zhang
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Zhang
authors.forename: Run-lei
authors.initials: RL
authors.lastname: Du
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000502:physiology*
chemical_list: D007976:Leupeptins; D051028:bcl-2-Associated X Protein; C063261:acetylleucyl-leucyl-norleucinal
keywords: ALLN; Anti-tumor; Apoptosis; Bax; CCK-8; Cell Counting Kit-8; Colon cancer; Mitochondria; N-acetyl-leu-leunorleucinal; PBS; PVDF; phosphate-buffered saline; polyvinylidene difluoride