The Cytotoxic Constituents of<i>Betula platyphylla</i>and their Effects on Human Lung A549 Cancer Cells

Yang, Eun‐Ju; An, Ju-Hee; Son, Youn Kyoung; Yeo, Joo‐Hong; Song, Kyung‐Sik

doi:10.20307/nps.2018.24.4.219

Cited by 9 publications

(7 citation statements)

References 37 publications

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“…Compounds 1 and 3, the two diarylheptanoids, presented significant cytotoxicity against the cells (Figure 4C,D). Consistently, the compounds 1 and 3 were previously reported to have cytotoxic acting on lung cancer cells [61].…”

Section: Discussionsupporting

confidence: 74%

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Activation of JNK and p38 in MCF-7 Cells and the In Vitro Anticancer Activity of Alnus hirsuta Extract

Ryu

Sung

et al. 2020

Molecules

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JNK and p38 are important mitogen-activated protein kinases (MAPKs) that respond to stress stimuli. The stress-activated MAPKs associated with apoptotic cell death play vital roles in mammalian cells. Alnus hirsuta, which contains abundant diarylheptanoids derivatives, is a valuable medicinal plant. The CHCl3 extract (AHC) containing platyphyllenone (1) and platyphyllone (3) as main compounds showed in vitro anticancer effects. We report the biological activities of A. hirsuta extract associated with the regulation of apoptosis and JNK and p38 in MCF-7 breast cancer cells. Levels of phospho-JNK and phospho-p38 by AHC treatment were evaluated by enzyme-linked immunosorbent assay (ELISA). ROS production, apoptotic effect, and DNA contents of the cells were measured by flow cytometry. The two diarylheptanoids 1 and 3 and the AHC extract exhibited cytotoxic effects on MCF-7 cells in MTT assay, with IC50 values of 18.1, 46.9, 260.0 μg/mL, respectively. AHC induced ROS generation and elevated the endogenous levels of phospho-JNK and phospho-p38. AHC resulted in apoptosis and cell cycle arrest. We suggest that the antitumor effect of A. hirsuta extract is achieved by apoptosis promotion and cell cycle arrest mediated by the activation of JNK and p38 signaling pathway via ROS generation.

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Section: Discussionsupporting

confidence: 74%

“…Although higher IC 50 values were shown, HeLa and Jurkat cells also presented cytotoxicity in MTT assay. A document on lung cancer cells support the anticancer activity of the two diarylheptanoids that we isolated from AHC [61]. Therefore, we can estimate the likelihood of activity as described above against these cells.…”

Section: Discussionmentioning

confidence: 75%

Activation of JNK and p38 in MCF-7 Cells and the In Vitro Anticancer Activity of Alnus hirsuta Extract

Ryu

Sung

et al. 2020

Molecules

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“…We investigated whether the isolated compounds 1–14 could inhibit the viability of A2780 human ovarian carcinoma cells. The MTT cell viability assays were performed with compounds 1 – 14 to determine their cytotoxic effects on A2780 cells [29,30,31,32]. Of the tested compounds, compounds 4 and 11 significantly suppressed cell proliferation in a concentration-dependent manner and compound 11, particularly, showed the strongest effect, with an IC 50 value of 44.47 ± 0.01 μM, whereas compounds 7 , 8 , 9 , and 12 weakly reduced the viability of A2780 cells at 50 μM.…”

Section: Resultsmentioning

confidence: 99%

Betulinic Acid Suppresses Ovarian Cancer Cell Proliferation through Induction of Apoptosis

Lee

Kang

et al. 2019

Biomolecules

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Ovarian cancer is one of the leading causes of cancer deaths worldwide in women, and the most malignant cancer among the different gynecological cancers. In this study, we explored potentially anticancer compounds from Cornus walteri (Cornaceae), the MeOH extract of which has been reported to show considerable cytotoxicity against several cancer cell lines. Phytochemical investigations of the MeOH extract of the stem and stem bark of C. walteri by extensive application of chromatographic techniques resulted in the isolation of 14 compounds (1–14). The isolated compounds were evaluated for inhibitory effects on the viability of A2780 human ovarian carcinoma cells and the underlying molecular mechanisms were investigated. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to assess the anticancer effects of compounds 1–14 on A2780 cells, which showed that compound 11 (betulinic acid) reduced the viability of these cells in a concentration-dependent manner and had an half maximal (50%) inhibitory concentration (IC50) of 44.47 μM at 24 h. Nuclear staining and image-based cytometric assay were carried out to detect the induction of apoptosis by betulinic acid. Betulinic acid significantly increased the condensation of nuclei and the percentage of apoptotic cells in a concentration-dependent manner in A2780 cells. Western blot analysis was performed to investigate the underlying mechanism of apoptosis. The results indicated that the expression levels of cleaved caspase-8, -3, -9, and Bax were increased in A2780 cells treated with betulinic acid, whereas those of Bcl-2 were decreased. Thus, we provide the experimental evidence that betulinic acid can induce apoptosis in A2780 cells through both mitochondria-dependent and -independent pathways and suggest the potential use of betulinic acid in the development of novel chemotherapeutics for ovarian cancer therapy.

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“…NIBR2016‐180). The isolation was carried out according to the previous paper (Yang, An, Son, Yeo, & Song, ). Briefly, BP (10 kg) was refluxed three times in MeOH for 6 hr.…”

Section: Methodsmentioning

confidence: 99%

1,7‐Bis(4‐hydroxyphenyl)‐4‐hepten‐3‐one from Betula platyphylla induces apoptosis by suppressing autophagy flux and activating the p38 pathway in lung cancer cells

Jung

Song

Son

et al. 2019

Phytotherapy Research

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Betula platyphylla (BP) is frequently administered in the treatment of various human diseases, including cancers. This study was undertaken to investigate the pharmacological function of the active components in BP and the underlying mechanism of its chemotherapeutic effects in human lung cancer cells. We observed that BP extracts and 1,7‐bis(4‐hydroxyphenyl)‐4‐hepten‐3‐one (BE1), one of the components of BP, effectively decreased the cell viability of several lung cancer cell lines. BE1‐treated cells exhibited apoptosis induction and cell cycle arrest at the G2/M phase. Further examination demonstrated that BE1 treatment resulted in suppression of autophagy, as evidenced by increased protein expression levels of both LC3 II and p62/SQSTM1. Interestingly, the pharmacological induction of autophagy with rapamycin remarkably reduced the BE1‐induced apoptosis, indicating that apoptosis induced by BE1 was associated with autophagy inhibition. Our data also demonstrated that BE1 exposure activated the p38 pathway resulting in regulation of the pro‐apoptotic activity. Taken together, we believe that BE1 is a potential anticancer agent for human lung cancer, which exerts its effect by enhancing apoptosis via regulating autophagy and the p38 pathway.

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The Cytotoxic Constituents ofBetula platyphyllaand their Effects on Human Lung A549 Cancer Cells

Cited by 9 publications

References 37 publications

Activation of JNK and p38 in MCF-7 Cells and the In Vitro Anticancer Activity of Alnus hirsuta Extract

Activation of JNK and p38 in MCF-7 Cells and the In Vitro Anticancer Activity of Alnus hirsuta Extract

Betulinic Acid Suppresses Ovarian Cancer Cell Proliferation through Induction of Apoptosis

1,7‐Bis(4‐hydroxyphenyl)‐4‐hepten‐3‐one from Betula platyphylla induces apoptosis by suppressing autophagy flux and activating the p38 pathway in lung cancer cells

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