Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (V): coumarins and alkaloids from Boenninghausenia japonica and Ruta graveolens

Nakano, Daisuke; Ishitsuka, Kenji; Matsuda, Narumi; Kouguchi, Ai; Tsuchihashi, Ryota; Okawa, Masafumi; Okabe, Hikaru; Tamura, Kazuo; Kinjo, Junei

doi:10.1007/s11418-016-1046-5

Cited by 7 publications

(8 citation statements)

References 34 publications

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“…On the other hand, the functional 5-methoxy group seemed to decrease cytotoxic efficiency of IPP in comparison with XN towards A549, H2170, RK45, and TE671 cells. The present results are consistent with previous reports suggesting that the presence of substituents attached to the benzene ring at positions C-5 and C-8 may be important for enhancing the anticancer properties of furanocoumarins [22,27,28].…”

Section: Discussionsupporting

confidence: 93%

Imperatorin as a Promising Chemotherapeutic Agent against Human Larynx Cancer and Rhabdomyosarcoma Cells

et al. 2020

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Naturally occurring coumarins are bioactive compounds widely used in Asian traditional medicine. They have been shown to inhibit proliferation, induce apoptosis, and/or enhance the cytotoxicity of currently used drugs against a variety of cancer cell types. The aim of our study was to examine the antiproliferative activity of different linear furanocoumarins on human rhabdomyosarcoma, lung, and larynx cancer cell lines, and dissolve their cellular mechanism of action. The coumarins were isolated from fruits of Angelica archangelica L. or Pastinaca sativa L., and separated using high-performance counter-current chromatography (HPCCC). The identity and purity of isolated compounds were confirmed by HPLC-DAD and NMR analyses. Cell viability and toxicity assessments were performed by means of methylthiazolyldiphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, respectively. Induction of apoptosis and cell cycle progression were measured using flow cytometry analysis. qPCR method was applied to detect changes in gene expression. Linear furanocoumarins in a dose-dependent manner inhibited proliferation of cancer cells with diverse activity regarding compounds and cancer cell type specificity. Imperatorin (IMP) exhibited the most potent growth inhibitory effects against human rhabdomyosarcoma and larynx cancer cell lines owing to inhibition of the cell cycle progression connected with specific changes in gene expression, including CDKN1A. As there are no specific chemotherapy treatments dedicated to laryngeal squamous cell carcinoma and rhabdomyosarcoma, and IMP seems to be non-toxic for normal cells, our results could open a new direction in the search for effective anti-cancer agents.

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Section: Discussionsupporting

confidence: 93%

Imperatorin as a Promising Chemotherapeutic Agent against Human Larynx Cancer and Rhabdomyosarcoma Cells

et al. 2020

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“…As we reported previously, 7) the extracts of A. curassavica showed potent activity against MT-1 (50% effective concentration (EC 50 ), aerial parts: 11.5 µg/mL, roots: 4.2 µg/mL) and MT-2 (EC 50 , aerial parts: 10.1 µg/mL, roots: 4.1 µg/mL) cells. Therefore, we attempted to isolate their active components.…”

Section: Resultssupporting

confidence: 74%

“…3) We previously reported the screening results of 459 extracts and the isolation of active constituents (withanolides, aporphine alkaloids, phenanthroindolizidine alkaloids, quinolone alkaloids and coumarins) against MT-1 and MT-2 cell lines. [4][5][6][7][8] Herein, following from the results of our previous screening program, 7) we report the isolation of cardenolides as active components from Asclepias curassavica. That belongs to the family Apocynaceae and includes cardenolides.…”

Section: Introductionmentioning

confidence: 99%

Screening of Promising Chemotherapeutic Candidates from Plants against Human Adult T-Cell Leukemia/Lymphoma (VI): Cardenolides from <i>Asclepias curassavica</i>

Nakano

Ishitsuka

Takashima

et al. 2020

Biological & Pharmaceutical Bulletin

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In the course of our screening program for novel chemotherapeutic candidates from plants against adult T-cell leukemia/lymphoma, the extracts of Asclepias curassavica L. showed potent activity against MT-1 and MT-2 cells. Therefore, we attempted to isolate their active components. We identified a new cardenolide, 19-dihydrocalactinic acid methyl ester (1), along with 16 known cardenolides (2-17). Their structures were determined on the basis of spectroscopic data. Almost all of the isolated cardenolides inhibited the growth of both tumor cell lines. All the doubly linked cardenolides (11-17) except for 14 showed more potent activity than the other cardenolides. A comparison of the activities of 11, 14 and 16 revealed that the presence of hydroxy or acetoxy functional groups at C-16 led to a decrease in the activity. The 50% effective concentration (EC 50) value of calotropin (11) against MT-2 cells was comparable to the potency of the clinical antineoplastic drug doxorubicin. The cytotoxic effect of 11 toward normal mononuclear cells obtained from the peripheral blood (PB-MNCs) was observed at a concentration 6 to 12 times higher than that used to induce growth inhibition against MT-1 and MT-2 cells. The proportions of annexin V-positive cells after 72 h of treatment with 11 were increased, indicating that it significantly induced apoptosis in MT-1 and MT-2 cells in a concentration-dependent manner. Cell cycle experiments demonstrated that 11 arrested MT-1 and MT-2 cells at the G2/M phase. Therefore, compound 11 may be a promising candidate for the treatment of adult T-cell leukemia/lymphoma.

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“…The Flavonoids are a group of bioactive compounds with high anti‐cancer ability that are extensively found in foodstuffs of plant origin. They are used broadly for the treatment of many cancers, containing breast, pancreatic, prostate, lung, ALL, bladder, and colorectal cancers (Gao, Liu, et al, ; Luo et al, ; Nakano et al, ; Saha, Kaushik, Das, Pal, & Majumder, ; Sak, Kasemaa, & Everaus, ; Shen et al, ; Tabrizi et al, ; Wang et al, ). The Flavonoid Rotenone interacts with electron transport and nicotinamide adenine dinucleotide hydride (NADH) during ATP formation.…”

Section: Intracellular Anti‐apoptotic Proteins As Targeted Therapymentioning

confidence: 99%

Down‐regulation of intracellular anti‐apoptotic proteins, particularly c‐FLIP by therapeutic agents; the novel view to overcome resistance to TRAIL

Hassanzadeh

Hagh

Alivand

et al. 2018

Journal Cellular Physiology

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a member of the tumor necrosis factor (TNF) superfamily that induces apoptosis in different types of cancer cells via activation of caspase cascade. TRAIL interacts with its cognate receptors that placed on cancer cells surface, including TRAIL-R1 (death receptor 4, DR4), TRAIL-R2 (death receptor 5, DR5), TRAIL-R3 (decoy receptor 1, DcR1), TRAIL-R4 (decoy receptor 2, DcR2), and osteoprotegerin (OPG). Despite high apoptosis-inducing ability of TRAIL, various cancerous cells gain resistance to TRAIL gradually, and consequently TRAIL potential for apoptosis stimulation in these cells diminishes intensely. According to diverse ranges of examinations, intracellular anti-apoptotic proteins, such as cellular-FLICE inhibitory protein (c-FLIP), apoptosis inhibitors (IAPs), myeloid cell leukemia sequence 1 (MCL-1), BCL-2, BCL-XL, and survivin play key role in cancer cells resistance to TRAIL. These proteins attenuate cancer cells sensitivity to TRAIL via various functions, importantly through caspase cascade suppression. The c-FLIP avoids from caspase 8 activation by FADD via binding to caspase 8 cleavage of FADD. Moreover, it activates signaling pathways that involved in cancer cells survival and proliferation. Intriguingly, it appears that the down-regulation of intracellular anti-apoptotic proteins, particularly c-FLIP is effectiveness goal for TRAIL-resistant cancers therapy, because their up-regulation in association with poor prognosis has been observed in various types of TRAIL-resistant cancers. In this review, we tried to collect and examine investigations that researchers have been able to sensitize cancer cells to TRAIL through targeting of c-FLIP alone or with other intracellular anti-apoptotic proteins directly or indirectly. It seems that co-treatment of resistant cells by TRAIL with other therapeutic agents with the aim of intracellular anti-apoptotic proteins inhibition is hopeful and attractive approach to overcome various TRAIL-resistant cancers.

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Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (V): coumarins and alkaloids from Boenninghausenia japonica and Ruta graveolens

Cited by 7 publications

References 34 publications

Imperatorin as a Promising Chemotherapeutic Agent against Human Larynx Cancer and Rhabdomyosarcoma Cells

Imperatorin as a Promising Chemotherapeutic Agent against Human Larynx Cancer and Rhabdomyosarcoma Cells

Screening of Promising Chemotherapeutic Candidates from Plants against Human Adult T-Cell Leukemia/Lymphoma (VI): Cardenolides from <i>Asclepias curassavica</i>

Down‐regulation of intracellular anti‐apoptotic proteins, particularly c‐FLIP by therapeutic agents; the novel view to overcome resistance to TRAIL

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