Screening of Promising Chemotherapeutic Candidates from Plants against Human Adult T-Cell Leukemia/Lymphoma (VII): Active Principles from Thuja occidentalis L.

Daisuke Nakano,Masafumi Okawa,Ryota Tsuchihashi,Kenji Ishitsuka,Junei Kinjo,Madoka Ishihara,Kazuo Tamura

doi:10.3390/molecules26247619

Daisuke Nakano, Masafumi Okawa + Show 5 more

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https://doi.org/10.3390/molecules26247619

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Abstract

During the screening of novel chemotherapeutic candidates from plants against adult T-cell leukemia/lymphoma, we identified that the extracts of Thuja occidentalis (Cupressaceae) showed potent anti-proliferative activity in MT-1 and MT-2 cells. Therefore, we attempted to isolate the active components from this plant. We isolated and identified 32 compounds (1–32; eight lignans, 18 terpenoids, and six flavonoids) from the extracts of the leaves and cones. Their structures were determined by spectroscopic analysis. Several of the isolated compounds inhibited the growth of both cell lines. Lignans showed more potent activity than other classes of compounds. A comparison of the activities of compounds 1–8 revealed that the presence of a trans-lactone (linkage of C-6 to C-7) correlated with increased activity. Diterpenes showed moderate activity, and the presence of a ketone moiety at the C-7 position correlated with increased activity in compounds 12–21. In addition, biflavones showed moderate activity, and the presence of methoxy functions appeared to influence the activity of these compounds. Several lignans were lead compound of anti-cancer reagent (etoposide). In conclusion, not only lignans, but also diterpenes and/or biflavones, may be promising candidates for the treatment of adult T-cell leukemia/lymphoma.

Highlights

Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature peripheral Tlymphocytes associated with human T-cell lymphotropic virus type I (HTLV-1)
MT-1 cells were established from the peripheral blood tumor cells of ATL patients [2], and MT-2 cells were established from cord blood T-cells by cocultivation of normal human cord lymphocytes and peripheral blood tumor cells from an ATL patient [3]
We previously reported the screening of 582 extracts and the isolation of active constituents for testing in MT-1 and MT-2 cell lines [4,5,6,7,8,9,10]

Summary

Introduction

Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature peripheral Tlymphocytes associated with human T-cell lymphotropic virus type I (HTLV-1). Conventional chemotherapeutic regimens used to treat other types of malignant lymphoma have been administered to ATL patients, but the therapeutic outcomes of acute- and lymphoma-type ATL remain very poor [1]. We conducted a search for novel chemotherapeutic candidates for the treatment of ATL in plant extracts and tested these compounds in two cell lines. We previously reported the screening of 582 extracts and the isolation of active constituents (withanolides, cardenolides, aporphine alkaloids, phenanthroindolizidine alkaloids, quinolone alkaloids, and coumarins) for testing in MT-1 and MT-2 cell lines [4,5,6,7,8,9,10].

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