Effect of Angelica gigas Nakai Ethanol Extract and Decursin on Human Pancreatic Cancer Cells

Kweon, Bitna; Han, Yohan; Kee, Ji‐Ye; Mun, Jeong‐Geon; Jeon, Hee Dong; Choi, Byung-Min; Hong, Seung‐Heon

doi:10.3390/molecules25092028

Cited by 12 publications

(12 citation statements)

References 34 publications

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“…Here, we evaluated the efficacy and associated mechanism of decursin for its anticancer activity against PCa cells. Decursin, a coumarin compound, was first isolated from the roots of Angelica gigas Nakai and has shown anticancer activity in various cancer types including PCa 17–21 . In our previous study, decursin was found to induce a G1 phase cell cycle arrest and apoptosis in PCa cells by modulating the levels of cyclin‐dependent kinases (CDKs), cyclins and CDK inhibitors 22 .…”

Section: Introductionmentioning

confidence: 99%

Decursin inhibits EGFR‐ERK1/2 signaling axis in advanced human prostate carcinoma cells

et al. 2023

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We have shown that decursin, a coumarin compound, induces cell cycle arrest and apoptosis in human prostate cancer cells (PCa); however, its molecular mechanisms are largely unexplored. We studied the mechanisms associated with its anticancer activity in advanced human prostate carcinoma cells. We found that decursin inhibited epidermal growth factor receptor (EGFR) signaling by inhibiting its activating phosphorylation at tyrosine 1068 residue in DU145 and 22Rv1 cells. This inhibition of EGFR was associated with the downregulation of ERK1/2 phosphorylation. Both EGFR and ERK1/2 are known to be deregulated/activated in many human malignancies. Consistent with our earlier study, decursin (25-100 µM) treatment for 24-72 h inhibited DU145 cell proliferation by 49%-87% (p < 0.001) which was associated with strong G1 phase arrest and cell death. It also decreased (p < 0.001) the number of surviving colonies. Decursin moderately increased the expression of Rb-related proteins p107 and p130 but decreased the levels of E2F family transcription factors including E2F-3, E2F-4 and E2F-5. Further, decursin strongly inhibited the growth of androgen-dependent prostate carcinoma 22Rv1 cells from 61% to 79% (p < 0.001) and arrested these cells at G1 phase via induction of cyclin-dependent kinase inhibitor p27/Kip1 and downregulation of CDK2 and CDK4 protein expression. Additionally, EGFR inhibitor erlotinib-and EGF ligand-modulated EGFR activation validated EGFR signaling as a target of decursin-mediated cell growth inhibition and cytotoxicity. Decursin decreased EGF ligand-induced phosphorylation of EGFR (Y-1068) as well as activation of its downstream mediator, ERK1/2. Furthermore, inhibitory targeting of EGFR-ERK1/2 axis by combinatorial treatment of decursin and erlotinib further sensitized DU145 cells for the decursin-induced growth inhibition and cell death. Overall, these findings strongly suggest that anticancer efficacy of decursin against human PCa involves inhibitory targeting of EGFR-ERK1/2 signaling axis, a pathway constitutively active in advanced PCa.

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Section: Introductionmentioning

confidence: 99%

Decursin inhibits EGFR‐ERK1/2 signaling axis in advanced human prostate carcinoma cells

et al. 2023

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“…Decursin also mediates apoptosis through the phosphorylation of JNK and p38 and the downregulation of Bcl-2, CDK4, and cyclin D1 in glioblastoma cells U87 [ 14 ]. The ethanol extract of Angelica gigas inhibits cell viability and colony formation and induces apoptosis and G0/G1 arrest via the inhibition of cyclin D1, CDK4, MMP-2, MMP-9, and p38 phosphorylation in the pancreatic cancer cells PANC-1 and PaCa-2 [ 15 ]. Traditional Chinese medicine DangguiBuxue Tang (DBT) exerts anti-cancer effects in colorectal cancer cells, and a combination of DBT and radiation has more powerful anticancer effects compared to radiation or DBT alone [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

The Herbal Formula JI017 Induces ER Stress via Nox4 in Breast Cancer Cells

Kim

2021

Antioxidants

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Chemotherapy is a powerful anti-tumor therapeutic strategy; however, resistance to treatment remains a serious concern. To overcome chemoresistance, combination therapy with anticancer drugs is a potential strategy. We developed a novel herbal extract, JI017, with lower toxicity and lesser side effects. JI017 induced programmed cell death and excessive unfolded protein response through the release of intracellular reactive oxygen species (ROS) and calcium in breast cancer cells. JI017 treatment increased the expression of endoplasmic reticulum (ER) stress markers, including p-PERK, p-eIF2α, ATF4, and CHOP, via the activation of both exosomal GRP78 and cell lysate GRP78. The ROS inhibitors diphenyleneiodonium and N-acetyl cysteine suppressed apoptosis and excessive ER stress by inhibiting Nox4 in JI017-treated breast cancer cells. Furthermore, in paclitaxel-resistant breast cancer cell lines, MCF-7R and MDA-MB-231R, a combination of JI017 and paclitaxel overcame paclitaxel resistance by blocking epithelial-mesenchymal transition (EMT) processes, such as the downregulation of E-cadherin expression and the upregulation of HIF-1α, vimentin, Snail, and Slug expression. These findings suggested that JI017 exerts a powerful anti-cancer effect in breast cancer and a combination therapy of JI017 and paclitaxel may be a potential cancer therapy for paclitaxel resistant breast cancer.

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“…JI017 is a combination of herbal extracts from Angelica gigas (Ag), Zingiber officinale Roscoe (Zo), and Aconitum carmichaeli (Ac) in the ratio of 2:1:1. The anti-cancer effects of Ag, Zo, and Ac individually have been well reported in many cancer cells, including pancreatic cancer, liver cancer, breast cancer, lung cancer, and oral cancer [9][10][11][12]. Ag ethanol extracts induce caspase-3-dependent apoptosis by inhibiting MMP-2 and MMP-9 in Human pancreatic cancer cells [9].…”

Section: Introductionmentioning

confidence: 99%

“…The anti-cancer effects of Ag, Zo, and Ac individually have been well reported in many cancer cells, including pancreatic cancer, liver cancer, breast cancer, lung cancer, and oral cancer [9][10][11][12]. Ag ethanol extracts induce caspase-3-dependent apoptosis by inhibiting MMP-2 and MMP-9 in Human pancreatic cancer cells [9]. Zo ethanol extracts mediate caspase-3-dependent apoptosis by activating autophagic cell death and cell cycle arrest [13].…”

Section: Introductionmentioning

confidence: 99%

JI017, a Complex Herbal Medication, Induces Apoptosis via the Nox4–PERK–CHOP Axis in Ovarian Cancer Cells

Kim

2021

IJMS

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Many anti-cancer drugs, including paclitaxel and etoposide, have originated and been developed from natural products, and traditional herbal medicines have fewer adverse effects and lesser toxicity than anti-tumor reagents. Therefore, we developed a novel complex herbal medicine, JI017, which mediates endoplasmic reticulum (ER) stress and apoptosis through the Nox4–PERK–CHOP signaling pathway in ovarian cancer cells. JI017 treatment increases the expression of GRP78, ATF4, and CHOP and the phosphorylation of PERK and eIF2α via the upregulation of Nox4. Furthermore, it increases the release of intracellular reactive oxygen species (ROS), the production of intracellular Ca2+, and the activation of exosomal GRP78 and cell lysate GRP78. Combination treatment using the sarco/endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin (TG) and JI017 reportedly induces increased ER stress and cell death in comparison to the control; however, knockdown experiments of PERK and CHOP indicated suppressed apoptosis and ER stress in JI017-treated ovarian cancer cells. Furthermore, targeting Nox4 using specific siRNA and pharmacological ROS inhibitors, including N-acetylcystein and diphenylene iodonium, blocked apoptosis and ER stress in JI017-treated ovarian cancer cells. In the radioresistant ovarian cancer model, when compared to JI017 alone, JI017 co-treatment with radiation induced greater cell death and resulted in overcoming radioresistance by inhibiting epithelial–mesenchymal-transition-related phenomena such as the reduction of E-cadherin and the increase of N-cadherin, vimentin, Slug, and Snail. These findings suggest that JI017 is a powerful anti-cancer drug for ovarian cancer treatment and that its combination treatment with radiation may be a novel therapeutic strategy for radioresistant ovarian cancer.

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Effect of Angelica gigas Nakai Ethanol Extract and Decursin on Human Pancreatic Cancer Cells

Cited by 12 publications

References 34 publications

Decursin inhibits EGFR‐ERK1/2 signaling axis in advanced human prostate carcinoma cells

Decursin inhibits EGFR‐ERK1/2 signaling axis in advanced human prostate carcinoma cells

The Herbal Formula JI017 Induces ER Stress via Nox4 in Breast Cancer Cells

JI017, a Complex Herbal Medication, Induces Apoptosis via the Nox4–PERK–CHOP Axis in Ovarian Cancer Cells

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