scholarly journals Relationship between triterpenoid anticancer drug resistance, autophagy, and caspase-1 in adult T-cell leukemia

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2026 ◽  
Author(s):  
Tsukasa Nakanishi ◽  
Yuan Song ◽  
Cuiying He ◽  
Duo Wang ◽  
Kentaro Morita ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
T Cell ◽  
Cord Blood Transplantation ◽  
B Cell Lymphoma ◽  
Human Leukemia ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Caspase 1

We previously reported that the inflammasome inhibitor cucurbitacin D (CuD) induces apoptosis in human leukemia cell lines. Here, we investigated the effects of CuD and a B-cell lymphoma extra-large (Bcl-xL) inhibitor on autophagy in peripheral blood lymphocytes (PBL) isolated from adult T-cell leukemia (ATL) patients. CuD induced PBL cell death in patients but not in healthy donors. This effect was not significantly inhibited by treatment with rapamycin or 3-methyladenine (3-MA). The Bcl-xL inhibitor Z36 induced death in primary cells from ATL patients including that induced by CuD treatment, effects that were partly inhibited by 3-MA. Similarly, cell death induced by the steroid prednisolone was enhanced in the presence of Z36. A western blot analysis revealed that Z36 also promoted CuD-induced poly(ADP ribose) polymerase cleavage. Interestingly, the effects of CuD and Z36 were attenuated in primary ATL patient cells obtained upon recurrence after umbilical cord blood transplantation, as compared to those obtained before chemotherapy. Furthermore, cells from this patient expressed a high level of caspase-1, and treatment with caspase-1 inhibitor-enhanced CuD-induced cell death. Taken together, these results suggest that rescue from resistance to steroid drugs can enhance chemotherapy, and that caspase-1 is a good marker for drug resistance in ATL patients.

SRT1720 induces SIRT1‐independent cell death in adult T‐cell leukemia/lymphoma

FEBS Journal ◽  
2022 ◽  
Author(s):  
Tomohiro Kozako ◽  
Naho Kato ◽  
Takeo Ohsugi ◽  
Yu‐ichiro Uchida ◽  
Makoto Yoshimitsu ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia

Cell death induced by dorsomorphin in adult T‐cell leukemia/lymphoma is AMPK‐independent

FEBS Journal ◽  
2020 ◽  
Vol 287 (18) ◽  
pp. 4005-4015
Author(s):  
Akiyoshi Aikawa ◽  
Tomohiro Kozako ◽  
Yuichiro Uchida ◽  
Makoto Yoshimitsu ◽  
Kenji Ishitsuka ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia

scholarly journals Genistein Induced Apoptotic Cell Death in Adult T-Cell Leukemia Cells through Estrogen Receptors

2010 ◽  
Vol 74 (10) ◽  
pp. 2113-2115 ◽  
Author(s):  
Masao YAMASAKI ◽  
Ayako MUKAI ◽  
Masayo OHBA ◽  
Yoshihiro MINE ◽  
Yoichi SAKAKIBARA ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Estrogen Receptors ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Leukemia Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia

Epstein-Barr virus (EBV) genome carrying monoclonal B-cell lymphoma in a patient with adult T-cell leukemia-lymphoma

1991 ◽  
Vol 15 (9) ◽  
pp. 837-846 ◽  
Author(s):  
Kensei Tobinai ◽  
Tomoko Ohtsu ◽  
Masaki Hayashi ◽  
Tomohiro Kinoshita ◽  
Yoshihiro Matsuno ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Restoration of ceramide de novo synthesis by the synthetic retinoid ST1926 as it induces adult T-cell leukemia cell death

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Botheina Ghandour ◽  
Claudio Pisano ◽  
Nadine Darwiche ◽  
Ghassan Dbaibo
Keyword(s):  
Cell Death ◽  
T Cell ◽  
De Novo ◽  
Leukemia Cell ◽  
T Cell Leukemia ◽  
Ceramide Synthase ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Synthetic Retinoid ◽  
Human T Cell

Abstract Ceramide (Cer) is a bioactive cellular lipid with compartmentalized and tightly regulated levels. Distinct metabolic pathways lead to the generation of Cer species with distinguishable roles in oncogenesis. Deregulation of Cer pathways has emerged as an important mechanism for acquired chemotherapeutic resistance. Adult T-cell leukemia (ATL) cells are defective in Cer synthesis. ATL is an aggressive neoplasm that develops following infection with human T-cell lymphotropic virus-1 (HTLV-1) where the viral oncogene Tax contributes to the pathogenesis of the disease. ATL cells, resistant to all-trans-retinoic acid, are sensitive to pharmacologically achievable concentrations of the synthetic retinoid ST1926. We studied the effects of ST1926 on Cer pathways in ATL cells. ST1926 treatment resulted in early Tax oncoprotein degradation in HTLV-1-treated cells. ST1926 induced cell death and a dose- and time-dependent accumulation of Cer in malignant T cells. The kinetics and degree of Cer production showed an early response upon ST1926 treatment. ST1926 enhanced de novo Cer synthesis via activation of ceramide synthase CerS(s) without inhibiting dihydroceramide desaturase, thereby accumulating Cer rather than the less bioactive dihydroceramide. Using labeling experiments with the unnatural 17-carbon sphinganine and measuring the generated Cer species, we showed that ST1926 preferentially induces the activities of a distinct set of CerS(s). We detected a delay in cell death response and interruption of Cer generation in response to ST1926 in Molt-4 cells overexpressing Bcl-2. These results highlight the potential role of ST1926 in inducing Cer levels, thus lowering the threshold for cell death in ATL cells.

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