Article
Author: Doki, Noriko ; Seki, Fumiya ; Hachiro, Yoshifumi ; Kanda, Risa ; Hara, Takahiko ; Yagi, Takuya ; Nuriya, Hideko ; Maki, Shojiro A ; Goyama, Susumu ; Kitamura, Toshio ; Miyashita, Kazuya ; Kagaya, Noritaka ; Shin-Ya, Kazuo ; Nakata, Chihiro ; Kitada, Nobuo ; Hoyano, Shota ; Higashi, Tomoya ; Najima, Yuho ; Takechi, Azusa ; Yoshida, Chihiro ; Kobayashi, Takeshi ; Toya, Takashi ; Tanegashima, Kosuke
T-cell acute lymphoblastic leukemia (T-ALL) is one of the most frequently occurring cancers in children and is associated with a poor prognosis. Here, we performed large-scale screening of natural compound libraries to identify potential drugs against T-ALL. We identified three low-molecular-weight compounds (auxarconjugatin-B, rumbrin, and lavendamycin) that inhibited the proliferation of the T-ALL cell line CCRF-CEM, but not that of the B lymphoma cell line Raji in a low concentration range. Among them, auxarconjugatin-B and rumbrin commonly contained a polyenyl 3-chloropyrrol in their chemical structure, therefore we chose auxarconjugatin-B for further analyses. Auxarconjugatin-B suppressed the in vitro growth of five human T-ALL cell lines and two T-ALL patient-derived cells, but not that of adult T-cell leukemia patient-derived cells. Cultured normal T cells were several-fold resistant to auxarconjugatin-B. Auxarconjugatin-B and its synthetic analogue Ra#37 depolarized the mitochondrial membrane potential of CCRF-CEM cells within 3 h of treatment. These compounds are promising seeds for developing novel anti-T-ALL drugs.