Anthocyanidins induce apoptosis in human promyelocytic leukemia cells: Structure-activity relationship and mechanisms involved

  • Authors:
    • De-Xing Hou
    • Takashi Ose
    • Shigang Lin
    • Kazuhiro Harazoro
    • Izumi Imamura
    • Mayumi Kubo
    • Takuhiro Uto
    • Norihiko Terahara
    • Makoto Yoshimoto
    • Makoto Fujii
  • View Affiliations

  • Published online on: September 1, 2003     https://doi.org/10.3892/ijo.23.3.705
  • Pages: 705-712
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Abstract

Anthocyanidins are the aglycon nucleuses of anthocyanins, which are reddish pigments widely spread in colored fruits and vegetables. To investigate their anti-cancer effect, induction of apoptosis was tested in human promyelocytic leukemia cells (HL-60), which is a valid model for testing antileukemic or general antitumoral compounds. Of six anthocyanidins representing the aglycons of most of anthocyanins, only those with an ortho-dihydroxyphenyl structure on the B-ring induce apoptosis, suggesting that the ortho-dihydroxyphenyl structure of anthocyanidins may contribute to the induction of apoptosis. Delphinidin, the most potent inducer, causes apoptosis in a time- and dose-dependent manner. The efficacious induction of apoptosis was observed at 100 µM for 6 h. Concomitant with the apoptosis, delphinidin stimulates JNK pathway activation including JNK phosphorylation and c-jun gene expression, and activates caspase-3. Antioxidants including N-acetyl-L-cysteine (NAC) and catalase effectively block delphinidin-induced JNK phosphorylation, caspase-3 activation, and DNA fragmentation. Moreover, anthocyanidins directly cause HL-60 cells to generate intracellular hydrogen peroxide. Thus, anthocyanidins may trigger an apoptotic death program through an oxidative stress-involved JNK signaling pathway. The induction of apoptosis by anthocyanins may be the pivotal mechanism by which its chemopreventive action against cancer is based.

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September 2003
Volume 23 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Hou D, Ose T, Lin S, Harazoro K, Imamura I, Kubo M, Uto T, Terahara N, Yoshimoto M, Fujii M, Fujii M, et al: Anthocyanidins induce apoptosis in human promyelocytic leukemia cells: Structure-activity relationship and mechanisms involved. Int J Oncol 23: 705-712, 2003
APA
Hou, D., Ose, T., Lin, S., Harazoro, K., Imamura, I., Kubo, M. ... Fujii, M. (2003). Anthocyanidins induce apoptosis in human promyelocytic leukemia cells: Structure-activity relationship and mechanisms involved. International Journal of Oncology, 23, 705-712. https://doi.org/10.3892/ijo.23.3.705
MLA
Hou, D., Ose, T., Lin, S., Harazoro, K., Imamura, I., Kubo, M., Uto, T., Terahara, N., Yoshimoto, M., Fujii, M."Anthocyanidins induce apoptosis in human promyelocytic leukemia cells: Structure-activity relationship and mechanisms involved". International Journal of Oncology 23.3 (2003): 705-712.
Chicago
Hou, D., Ose, T., Lin, S., Harazoro, K., Imamura, I., Kubo, M., Uto, T., Terahara, N., Yoshimoto, M., Fujii, M."Anthocyanidins induce apoptosis in human promyelocytic leukemia cells: Structure-activity relationship and mechanisms involved". International Journal of Oncology 23, no. 3 (2003): 705-712. https://doi.org/10.3892/ijo.23.3.705