Antitumor agent yatein from Calocedrus formosana Florin leaf induces apoptosis in non-small-cell lung cancer cells

Ho, Shang Tse; Lin, Chi Chen; Wu, Tung Lin; Tung, Yu Tang; Wu, June H.

doi:10.1186/s10086-019-1838-9

Cited by 5 publications

(9 citation statements)

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“…Accordingly, we found that yatein treatment increased Wee1 expression in CL1-5 cells, indicating that Wee1 played a crucial role in the regulation of G 2 /M cell-cycle distribution in CL1-5 cells in the context of yatein treatment. On the other hand, we also found yatein is able to induce ROS production in A549 and CL1-5 cells in our previous study [15], suggesting that yatein may induce the oxidative DNA damage. Moreover, our previous results also revealed that the CL1-5 cells were more sensitive for the ROS production than the A549 cells after yatein treatment [15].…”

Section: Discussionsupporting

confidence: 63%

“…On the other hand, we also found yatein is able to induce ROS production in A549 and CL1-5 cells in our previous study [15], suggesting that yatein may induce the oxidative DNA damage. Moreover, our previous results also revealed that the CL1-5 cells were more sensitive for the ROS production than the A549 cells after yatein treatment [15].…”

Section: Discussionsupporting

confidence: 63%

“…In the present study, we found that yatein induced G 2 /M cell-cycle arrest in A549 and CL1-5 cells at the first 24 h treatment. Additionally, treatment with yatein for 48 h induced a dose-dependent increase in both early and late stage apoptosis in the A549 and CL1-5 cells [15]. As previously reported, some lignan compounds can inhibit cancer cell growth by inducing cell-cycle arrest.…”

Section: Discussionmentioning

confidence: 58%

“…According to our previous study [15], the IC 50 values for the 24 h yatein treatment in the A549 and CL1-5 cells were 10.0 and 2.1 μM, respectively. In addition, yatein exhibited excellent growth inhibitory effect in the A549 (IC 50 values = 3.5 μM) and CL1-5 cells (IC 50 values = 1.9 μM) after 72 h treatment.…”

Section: Discussionmentioning

confidence: 84%

“…Calocedrus formosana is a valuable softwood species in Taiwan, which not only has high industrial economic value but also exhibits multiple bioactivities [5,6,7,8,9,10,11,12,13,14]. We previously found that the C. formosana extract and its active phytocompound, yatein, inhibited the growth of human lung adenocarcinoma A549 and CL1-5 cells by inducing caspase-related apoptosis [15]. However, whether yatein regulates the cell cycle in human lung adenocarcinoma remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Mechanisms Underlying Yatein-Induced Cell-Cycle Arrest and Microtubule Destabilization in Human Lung Adenocarcinoma Cells

Lin

Tung

et al. 2019

Cancers

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Yatein is an antitumor agent isolated from Calocedrus formosana Florin leaves extract. In our previous study, we found that yatein inhibited the growth of human lung adenocarcinoma A549 and CL1-5 cells by inducing intrinsic and extrinsic apoptotic pathways. To further uncover the effects and mechanisms of yatein-induced inhibition on A549 and CL1-5 cell growth, we evaluated yatein-mediated antitumor activity in vivo and the regulatory effects of yatein on cell-cycle progression and microtubule dynamics. Flow cytometry and western blotting revealed that yatein induces G2/M arrest in A549 and CL1-5 cells. Yatein also destabilized microtubules and interfered with microtubule dynamics in the two cell lines. Furthermore, we evaluated the antitumor activity of yatein in vivo using a xenograft mouse model and found that yatein treatment altered cyclin B/Cdc2 complex expression and significantly inhibited tumor growth. Taken together, our results suggested that yatein effectively inhibited the growth of A549 and CL1-5 cells possibly by disrupting cell-cycle progression and microtubule dynamics.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

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Molecular Mechanisms Underlying Yatein-Induced Cell-Cycle Arrest and Microtubule Destabilization in Human Lung Adenocarcinoma Cells

Lin

Tung

et al. 2019

Cancers

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Two O-Methyltransferases from Phylogenetically Unrelated Cow Parsley (Anthriscus sylvestris) and Hinoki-Asunaro (Thujopsis dolabrata var. hondae) as a Signature of Lineage-Specific Evolution in Lignan Biosynthesis

Yamamura

Kumatani

Shiraishi

et al. 2022

Plant and Cell Physiology

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O-Methyltransferases (OMTs) play important roles in antitumor lignan biosynthesis. To date, six OMTs catalyzing the methylation of dibenzylbutyrolactone lignans as biosynthetic precursors of antitumor lignans have been identified. However, there is still no systematic understanding of the diversity and regularity of the biosynthetic mechanisms among various plant lineages. Herein, we report the characterization of two OMTs from Anthriscus sylvestris and Thujopsis dolabrata var. hondae [designated as AsSecoNorYatein (SNY) OMT and TdSNYOMT] together with the six known OMTs to evaluate their diversity and regularity. Although AsSNYOMT and TdSNYOMT accept 5-O-methylthujaplicatin and 4-O-demethylyatein as substrates, phylogenetic analysis indicated that these two OMTs shared low amino acid sequence identity, 33.8%, indicating a signature of parallel evolution. The OMTs and the six previously identified OMTs were found to be diverse in terms of their substrate specificity, regioselectivity, and amino acid sequence identity, indicating independent evolution in each plant species. Meanwhile, two-entropy analysis detected four amino acid residues as being specifically acquired by dibenzylbutyrolactone lignan OMTs. Site-directed mutation of AsSNYOMT indicated that two of them contributed specifically to 5-O-methylthujaplicatin methylation. The results provide a new example of parallel evolution and the diversity and regularity of OMTs in plant secondary (specialized) metabolism.

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Potential natural hydrosol blend TGLON suppresses the proliferation of five cancer cell lines and also ameliorates idiopathic pulmonary fibrosis in mouse model

Huang,

Chang,

Lin

et al. 2024

Preprint

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Background: Previous studies on natural substances for tumor cell inhibition have predominantly concentrated on efficacy, often overlooking safety concerns. This research utilizes "The Greatest Love of Nature (TGLON), a proprietary blend of plant hydrosols, to investigate its potential inhibitory effects on a variety of cancer cell lines while ensuring its relative safety to normal lung cells (MRC-5). Furthermore, initial animal studies have demonstrated that TGLON can mitigate the progression of idiopathic pulmonary fibrosis without acute oral toxicity, underscoring its potential utility as a nutritional supplement. Methods: TGLON, a hydrosol blend developed with specific proportions, underwent initial validation for its constituent composition and safety profile. The blend capacity to inhibit five different tumor cell types and alleviate pulmonary fibrosis was evaluated using cell viability assays and controlled animal experiments. Results: Dosages were determined to be safe at dilutions greater than 80-fold. At this concentration, TGLON exhibited inhibitory effects on 40.7% of lung cancer cells, 84% of liver cancer cells, 49.8% of breast cancer cells, 38% of stomach cancer cells, and inhibited 52% of leukemic lymphoblasts at a 200-fold dilution. Oral administration of TGLON was found to be safe and effective in reducing Bleomycin-induced pulmonary fibrosis in animal models. Conclusions:Under conditions deemed relatively safe, TGLON demonstrates bioactive properties, such as inhibiting five distinct types of human tumor cells and alleviating pulmonary fibrosis in animal models. These findings highlight its substantial potential as a nutritional supplement for improving overall patient health.

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Antitumor agent yatein from Calocedrus formosana Florin leaf induces apoptosis in non-small-cell lung cancer cells

Cited by 5 publications

References 35 publications

Molecular Mechanisms Underlying Yatein-Induced Cell-Cycle Arrest and Microtubule Destabilization in Human Lung Adenocarcinoma Cells

Molecular Mechanisms Underlying Yatein-Induced Cell-Cycle Arrest and Microtubule Destabilization in Human Lung Adenocarcinoma Cells

Two O-Methyltransferases from Phylogenetically Unrelated Cow Parsley (Anthriscus sylvestris) and Hinoki-Asunaro (Thujopsis dolabrata var. hondae) as a Signature of Lineage-Specific Evolution in Lignan Biosynthesis

Potential natural hydrosol blend TGLON suppresses the proliferation of five cancer cell lines and also ameliorates idiopathic pulmonary fibrosis in mouse model

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