Hinokitiol induces autophagy in murine breast and colorectal cancer cells

Wang, Wei-Kuang; Lin, Song-Tao; Chang, Wen‐Wei; Liu, Liwen; Li, Tom Yu-Tung; Kuo, Chun-Yu; Hsieh, Jeng-Long; Lee, Che‐Hsin

doi:10.1002/tox.22023

Cited by 35 publications

(39 citation statements)

References 19 publications

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“…It is a naturally occurring, aromatic, seven-membered tropolone compound. It has been reported to have applications in regulating several biological properties [24,25,35], and has also been shown to have inhibitory effects in several cancer cell lines [24,36,37]. In previous studies, the effective dose of hinokitiol against cancer cells ranged from 5 to 200 μM [37].…”

Section: Resultsmentioning

confidence: 99%

Hinokitiol-Loaded Mesoporous Calcium Silicate Nanoparticles Induce Apoptotic Cell Death through Regulation of the Function of MDR1 in Lung Adenocarcinoma Cells

Shie

et al. 2016

Materials

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Hinokitiol is a tropolone-related compound found in heartwood cupressaceous plants. Hinokitiol slows the growth of a variety of cancers through inhibition of cell proliferation. The low water solubility of hinokitiol leads to less bioavailability. This has been highlighted as a major limiting factor. In this study, mesoporous calcium silicate (MCS) nanoparticles, both pure and hinokitiol-loaded, were synthesized and their effects on A549 cells were analyzed. The results indicate that Hino-MCS nanoparticles induce apoptosis in higher concentration loads (>12.5 μg/mL) for A549 cells. Hino-MCS nanoparticles suppress gene and protein expression levels of multiple drug resistance protein 1 (MDR1). In addition, both the activity and the expression levels of caspase-3/-9 were measured in Hino-MCS nanoparticle-treated A549 cells. The Hino-MCS nanoparticles-triggered apoptosis was blocked by inhibitors of pan-caspase, caspase-3/-9, and antioxidant agents (N-acetylcysteine; NAC). The Hino-MCS nanoparticles enhance reactive oxygen species production and the protein expression levels of caspase-3/-9. Our data suggest that Hino-MCS nanoparticles trigger an intrinsic apoptotic pathway through regulating the function of MDR1 and the production of reactive oxygen species in A549 cells. Therefore, we believe that Hino-MCS nanoparticles may be efficacious in the treatment of drug-resistant human lung cancer in the future.

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Section: Resultsmentioning

confidence: 99%

Hinokitiol-Loaded Mesoporous Calcium Silicate Nanoparticles Induce Apoptotic Cell Death through Regulation of the Function of MDR1 in Lung Adenocarcinoma Cells

Shie

et al. 2016

Materials

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“…Hinokitiol was also indicated to cause caspase-dependent apoptosis (16) and differentiation (17) in teratocarcinoma F9 cells. A recent study indicated that hinokitiol induced autophagy in murine breast and colorectal cancer cells via downregulation of the v-akt murine thymoma viral oncogene homolog 1/mechanistic target of rapamycin (serine/threonine kinase) signaling pathway, which led to cell death (18). Although the anti-tumor activity of hinokitiol has been reported, its effect on CSCs remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have suggested that enhancing the degradation of EGFR may provide a promising approach in cancer treatment (25). It has additionally been demonstrated that hinokitiol is able to cause death of breast cancer cells via induction of autophagy (18). Huang et al (40) demonstrated that hinokitiol may inhibit the expression of matrix metalloprotease-1 through the reduction of nuclear factor-κB (NF-κB) activation, resulting in the suppression of metastasis in a mouse melanoma model.…”

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confidence: 99%

Hinokitiol inhibits vasculogenic mimicry activity of breast cancer stem/progenitor cells through proteasome-mediated degradation of epidermal growth factor receptor

Lee

et al. 2016

Oncology Letters

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Abstract. Hinokitiol, alternatively known as β-thujaplicin, is a tropolone-associated natural compound with antimicrobial, anti-inflammatory and antitumor activity. Breast cancer stem/progenitor cells (BCSCs) are a subpopulation of breast cancer cells associated with tumor initiation, chemoresistance and metastatic behavior, and may be enriched by mammosphere cultivation. Previous studies have demonstrated that BCSCs exhibit vasculogenic mimicry (VM) activity via the epidermal growth factor receptor (EGFR) signaling pathway. The present study investigated the anti-VM activity of hinokitiol in BCSCs. At a concentration below the half maximal inhibitory concentration, hinokitiol inhibited VM formation of mammosphere cells derived from two human breast cancer cell lines. Hinokitiol was additionally indicated to downregulate EGFR protein expression in mammosphere-forming BCSCs without affecting the expression of messenger RNA. The protein stability of EGFR in BCSCs was also decreased by hinokitiol. The EGFR protein expression and VM formation capability of hinokitiol-treated BCSCs were restored by co-treatment with MG132, a proteasome inhibitor. In conclusion, the present study indicated that hinokitiol may inhibit the VM activity of BCSCs through stimulating proteasome-mediated EGFR degradation. Hinokitiol may act as an anti-VM agent, and may be useful for the development of novel breast cancer therapeutic agents. IntroductionCancer stem/progenitor cells (CSCs) are a subpopulation of cancer cells with the characteristics of tumor initiation (1), resistance to therapy (2) and metastasis (3). In breast cancer, breast CSCs (BCSCs) have been identified as cells with cluster of differentiation (CD)24 -CD44 + surface markers (4) or with high intracellular aldehyde dehydrogenase activity (5). BCSCs may additionally be enriched by cultivation in a serum-free, non-adherent environment, known as the mammosphere, which is a floating clump composed of breast cancer cells (6,7). In addition to tumor initiation and chemoresistant properties, BCSCs have also been indicated to exhibit vasculogenic mimicry (VM) activity (8), defined as the formation of perfusable, matrix-rich and vasculogenic-like networks by tumor cells, without involvement of endothelial cells (9). A previous study demonstrated that the VM activity of BCSCs is regulated by epidermal growth factor receptor (EGFR) signaling (8).Hinokitiol, alternatively known as β-thujaplicin, is a tropolone-associated natural compound isolated from heartwood cupressaceous plants (10), and has been widely used as an antimicrobial agent in toothpastes, cosmetics and food (11). In addition to antimicrobial activity, hinokitiol has been reported to possess anti-inflammatory (12,13) and antitumor Hinokitiol inhibits vasculogenic mimicry activity of breast cancer stem/progenitor cells through proteasome-mediated degradation of epidermal growth factor receptor

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“…Sua capacidade de agir na caspase-9 faz com que haja bloqueio no ciclo celular; ainda, o composto induz dois tipos de morte celular, tanto por apoptose, quanto por autofagia, por meio da ativação da via de sinalização Akt/mTOR, o que reduz o crescimento celular in vitro das células de câncer de mama e câncer colorretal (WANG et al 2016). …”

Section: Hinokitiolunclassified

“…Já a nobiletina, um flavonóide natural encontrado na casca das frutas cítricas como a tangerina, possui atividade angiogênica conhecida e, em células MCF-7, foi capaz de inibir a angiogênese tumoral (WANG et al 2016).…”

Section: Outras Substâncias Com Importante Papel No Tratamento Do Cânunclassified

Quimioterapia, Hormonioterapia E Novas Alternativas De Tratamento Do Adenocarcinoma Mamário

Gabriel¹,

Nepomuceno²,

Pimenta³

et al. 2017

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RESUMOO câncer de mama é um importante problema de saúde pública, com altas taxas de mortalidade relacionadas ao diagnóstico tardio. Vários são os fatores de risco que levam ao aparecimento do tumor, e as mulheres são mais frequentemente acometidas, principalmente em idade superior aos 50 anos. O tratamento de escolha é a remoção cirúrgica do tumor, radioterapia, quimioterapia e hormonioterapia, com objetivo de promover morte das células tumorais. Os tratamentos quimioterápico e hormonioterápico estão associados a uma alta incidência de efeitos adversos, o que compromete o tratamento, por reduzir a qualidade de vida da paciente. Essa incidência de reações adversas justifica a constante busca por novas formas de tratamento, que tenham ação mais seletiva, melhorando a expectativa de vida dos pacientes e as perspectivas de tratamento. PALAVRAS-CHAVE: câncer de mama, fitoterápicos, quimioterapia. CHEMOTHERAPY, HORMONIOTHERAPY AND NEW ALTERNATIVES FORTREATMENT OF MAMMARY ADENOCARCINOMA ABSTRACT Breast cancer is an important public health problem, with high mortality rates related to late diagnosis. Several are the risk factors that lead to the appearance of the tumor, and women are most frequently affected, especially in the age of 50 years. The treatment of choice is the surgical removal of the tumor, radiotherapy, chemotherapy and hormone therapy, with the goal of promoting tumor cell death. The chemotherapeutic and hormone therapy treatments are associated with a high

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Hinokitiol induces autophagy in murine breast and colorectal cancer cells

Cited by 35 publications

References 19 publications

Hinokitiol-Loaded Mesoporous Calcium Silicate Nanoparticles Induce Apoptotic Cell Death through Regulation of the Function of MDR1 in Lung Adenocarcinoma Cells

Hinokitiol-Loaded Mesoporous Calcium Silicate Nanoparticles Induce Apoptotic Cell Death through Regulation of the Function of MDR1 in Lung Adenocarcinoma Cells

Hinokitiol inhibits vasculogenic mimicry activity of breast cancer stem/progenitor cells through proteasome-mediated degradation of epidermal growth factor receptor

Quimioterapia, Hormonioterapia E Novas Alternativas De Tratamento Do Adenocarcinoma Mamário

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