Honokiol exhibits enhanced antitumor effects with chloroquine by inducing cell death and inhibiting autophagy in human non-small cell lung cancer cells.

Abstract:

:Honokiol (HNK), a potential antitumor compound, has been widely studied in recent years. It induces apoptosis and affects autophagy in cancer cells, yet the mechanism of its antitumor efficacy remains obscure. Chloroquine (CQ), an autophagy inhibitor, is often applied to sensitize antitumor drugs in clinical trials. Here, we investigated the antitumor effect of HNK or CQ alone or in combination in non-small cell lung cancer (NSCLC) cells. Using an experimental approach, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) or sulforhodamine B (SRB) was used to determine the cytotoxicity of the agents. The expression levels of proteins were detected by western blotting. Apoptosis was examined via Annexin V-FITC and PI staining. H460 cell xenografts in nude mice were used to study the effects of HNK and/or CQ in vivo. Transfection with siRNA was applied to knock down cathepsin D. The results demonstrated the enhanced effects of HNK combined with CQ on the inhibition of proliferation, induction of apoptosis in vitro and the reduction in growth in vivo. It was confirmed that HNK and/or CQ triggered apoptosis via a caspase-dependent manner. Furthermore, HNK significantly increased the expression of p62 and LC3-Ⅱ in the A549 and H460 cells and inhibited autophagy and induced apoptosis in a cathepsin D-involved manner. In conclusion, an enhanced antitumor effect was demonstrated following treatment with HNK combined with CQ by inhibiting autophagy and inducing apoptosis via a caspase-dependent and cathepsin D-involved manner. This combination may be a novel and useful antitumor approach for chemotherapy in NSCLC.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Lv X,Liu F,Shang Y,Chen SZ

doi

10.3892/or.2015.4091

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

1289-300

issue

3

eissn

1021-335X

issn

1791-2431

journal_volume

34

pub_type

杂志文章
  • A novel immunotherapeutic modality with direct hemoperfusion targeting transforming growth factor-beta prolongs the survival of tumor-bearing rats.

    abstract::Immune responses are frequently depressed in patients with cancer. One of the reasons for a poor immune response is the presence of increased levels of immunosuppressive substances associated with tumor growth. Transforming growth factor-beta (TGF-beta), a representative immunosuppressive cytokine, plays various roles...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Yamamoto Y,Ueda Y,Itoh T,Iwamoto A,Yamagishi H,Shimagaki M,Teramoto K

    更新日期:2006-12-01 00:00:00

  • Histone deacetylase 4 increases progressive epithelial ovarian cancer cells via repression of p21 on fibrillar collagen matrices.

    abstract::Histone deacetylase (HDAC) 4 is an emerging target in cancer therapeutics, but little is known about the function of HDAC4 in gynecologic malignancies. Therefore we investigated the mechanism of HDAC4 promoting the proliferation of epithelial ovarian cancer cells (OV). In this study, we observed that the proliferation...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4423

    authors: Shen YF,Wei AM,Kou Q,Zhu QY,Zhang L

    更新日期:2016-02-01 00:00:00

  • NF-YA promotes invasion and angiogenesis by upregulating EZH2-STAT3 signaling in human melanoma cells.

    abstract::The process of angiogenesis is essential for tumor development and metastasis. Vascular endothelial growth factor (VEGF), which is overexpressed in most human cancers, has been demonstrated to be a major modulator of angiogenesis. Thus, inhibition of VEGF signaling has the potential for tumor anti-angiogenic therapy. ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4761

    authors: Xu Z,Sun Y,Guo Y,Qin G,Mu S,Fan R,Wang B,Gao W,Wu H,Wang G,Zhang Z

    更新日期:2016-06-01 00:00:00

  • A polymorphism C3435T of the MDR-1 gene associated with smoking or high body mass index increases the risk of sporadic breast cancer in women.

    abstract::The human multidrug resistance gene 1 (MDR-1) encodes a plasma membrane P-glycoprotein (P-gp) that functions as the transmembrane efflux pump for various structurally unrelated anticancer agents and toxins. Polymorphisms in the MDR-1 gene may have an impact on the expression and function of P-gp, thereby influencing t...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Zubor P,Lasabova Z,Hatok J,Stanclova A,Danko J

    更新日期:2007-07-01 00:00:00

  • Potential for molecular targeted therapy of HER-2/neu for invasive bladder cancer: examination of gene amplification by fluorescence in situ hybridization.

    abstract::Analysis of HER-2/neu gene amplification by fluorescence in situ hybridization was performed in 40 patients with invasive bladder cancer in order to evaluate the potential for molecular targeted therapy of HER-2 as a tailor-made treatment for patients with invasive bladder cancer. This study included 40 patients seen ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Yamada Y,Naruse K,Nakamura K,Aoki S,Taki T,Tobiume M,Zennami K,Katsuda R,Hirano M,Hayashida K,Mizumukai E,Nanaura H,Honda N

    更新日期:2007-11-01 00:00:00

  • Actin-like protein 6A is a novel prognostic indicator promoting invasion and metastasis in osteosarcoma.

    abstract::Osteosarcoma harbors highly metastatic properties, accounting for postoperative recurrence and metastasis. Actin-like protein 6A (ACTL6A) regulates cell proliferation, migration and differentiation. However, the biologic role of ACTL6A in osteosarcoma remains unknown. In this study, the results showed that, by analysi...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5473

    authors: Sun W,Wang W,Lei J,Li H,Wu Y

    更新日期:2017-04-01 00:00:00

  • Withaferin A inhibits matrix metalloproteinase-9 activity by suppressing the Akt signaling pathway.

    abstract::Withaferin A (Wit A), a steroidal lactone isolated from Withania somnifera, exhibits anti-inflammatory, immuno-modulatory and anti-angiogenic properties and antitumor activities. In the present study, we investigated the effects of Wit A on protease-mediated invasiveness of the human metastatic cancer cell lines Caski...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2487

    authors: Lee DH,Lim IH,Sung EG,Kim JY,Song IH,Park YK,Lee TJ

    更新日期:2013-08-01 00:00:00

  • Mutational analysis of Smad7 in human cervical cancer.

    abstract::Our aim was to carry out mutational analysis of Smad7 exon 4 that codes for the Smad7 MH2 domain in human cervical cancer tissues. This study is warranted since genetic abnormalities of components of the transforming growth factor-beta (TGF-beta)/Smad signaling system have been implicated in a variety of human cancers...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000315

    authors: Hariharan R,Babu JM,P R,Pillai MR

    更新日期:2009-04-01 00:00:00

  • Anti-oxidative and hepatoprotective effects of lithospermic acid against carbon tetrachloride-induced liver oxidative damage in vitro and in vivo.

    abstract::Accumulation of an excess amount of reactive oxygen species (ROS) can cause hepatotoxicity that may result in liver damage. Therefore, development of anti-oxidative agents is needed for reducing liver toxicity. This study investigated the anti-oxidative and hepatoprotective activity of lithospermic acid, a plant-deriv...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4068

    authors: Chan KW,Ho WS

    更新日期:2015-08-01 00:00:00

  • Trastuzumab and docetaxel in a preclinical organotypic breast cancer model using tissue slices from mammary fat pad: Translational relevance.

    abstract::With the ever-increasing number of drugs approved to treat cancers, selection of the optimal treatment regimen for an individual patient is challenging. Breast cancer complexity requires novel predictive methods and tools. In the present study, we set up experimental conditions to obtain an 'ex vivo' organotypic cultu...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4074

    authors: Vesci L,Carollo V,Roscilli G,Aurisicchio L,Ferrara FF,Spagnoli L,De Santis R

    更新日期:2015-09-01 00:00:00

  • Sanguinarine-induced apoptosis in lung adenocarcinoma cells is dependent on reactive oxygen species production and endoplasmic reticulum stress.

    abstract::Sanguinarine (SAN), an alkaloid isolated from plants of the Papaveraceae family, is a compound with multiple biological activities. In the present study, we explored the anticancer properties of SAN in lung cancer using the human lung adenocarcinoma cell line SPC-A1. Our results revealed that SAN inhibited SPC-A1 cell...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4054

    authors: Gu S,Yang XC,Xiang XY,Wu Y,Zhang Y,Yan XY,Xue YN,Sun LK,Shao GG

    更新日期:2015-08-01 00:00:00

  • Plumbagin reduces chronic lymphocytic leukemia cell survival by downregulation of Bcl-2 but upregulation of the Bax protein level.

    abstract::Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and mainly originates from an accumulation of abnormal B cells caused by the dysregulation of cell proliferation and apoptosis rates. The aberration of apoptosis-related genes in CLL cells results in defective apoptosis of CLL cells i...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4950

    authors: Fu C,Gong Y,Shi X,Sun Z,Niu M,Sang W,Xu L,Zhu F,Wang Y,Xu K

    更新日期:2016-09-01 00:00:00

  • miR‑21 inhibitor facilitates the anticancer activity of doxorubicin loaded nanometer in melanoma.

    abstract::MicroRNA‑21 (miR‑21) is a potential therapeutic target for melanoma. Whether miR‑21 inhibitor affects the anti‑cancer activity of doxorubicin assisted by c(RGDyK)‑modified liposome (DLN) in melanoma and the underlying mechanisms are largely unknown. In this study, in vitro and animal models were used to explore the ef...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.7167

    authors: Wei X,You X,Zhang J,Zhou C

    更新日期:2019-07-01 00:00:00

  • Specific role of JNK in the maintenance of the tumor-initiating capacity of A549 human non-small cell lung cancer cells.

    abstract::Deregulation of c-Jun NH2-terminal kinase (JNK) signaling is now increasingly reported in a variety of human malignancies. Non-small cell lung cancer (NSCLC) is among such human malignancies with aberrant JNK activation; yet the exact role(s) of JNK deregulation in NSCLC biology, in particular in vivo, remains unclear...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2655

    authors: Okada M,Shibuya K,Sato A,Seino S,Watanabe E,Suzuki S,Seino M,Kitanaka C

    更新日期:2013-10-01 00:00:00

  • Alteration of CD4 T cell subsets in metastatic lymph nodes of human gastric cancer.

    abstract::Studies of tumor-infiltrating immune cells have revealed that immune escape plays an important role in tumor growth. The aim of the present study was to investigate the impact of metastasis affecting CD4+ T cell subsets in human clinical samples. Single-cell suspensions derived from tumor-draining lymph node (TDLN) an...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4064

    authors: Okita Y,Ohira M,Tanaka H,Tokumoto M,Go Y,Sakurai K,Toyokawa T,Kubo N,Muguruma K,Sawada T,Maeda K,Hirakawa K

    更新日期:2015-08-01 00:00:00

  • Loss of heterozygosity of nucleotide excision repair factors in sporadic oral squamous cell carcinoma using microdissected tissue.

    abstract::The deficiencies of nucleotide excision repair (NER) factors are involved in rare genetic diseases such as xeroderma pigmentosum (XP) with increased risk of developing cancer on sun-exposed areas of the skin. However, the abnormality of NER factors in human sporadic carcinoma remains unclear. Loss of heterozygosity (L...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.8.5.1133

    authors: Miyashita H,Mori S,Tanda N,Nakayama K,Kanzaki A,Sato A,Morikawa H,Motegi K,Takebayashi Y,Fukumoto M

    更新日期:2001-09-01 00:00:00

  • Umbilical cord-derived mesenchymal stem cells promote proliferation and migration in MCF-7 and MDA-MB-231 breast cancer cells through activation of the ERK pathway.

    abstract::Mesenchymal stem cells (MSCs) are known to migrate to tumor tissues and to play an important role in cancer progression. However, the effects of MSCs on tumor progression remain controversial. The purpose of the present study was to detect the effects of human umbilical cord-derived MSCs (hUC‑MSCs) on the human breast...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4109

    authors: Li T,Zhang C,Ding Y,Zhai W,Liu K,Bu F,Tu T,Sun L,Zhu W,Zhou F,Qi W,Hu J,Chen H,Sun X

    更新日期:2015-09-01 00:00:00

  • Tropomodulin 3 promotes liver cancer progression by activating the MAPK/ERK signaling pathway.

    abstract::Tropomodulin 3 (TMOD3) is a member of the pointed‑end capping protein family that contributes to invasion and metastasis in several types of malignancies. TMOD3 has been found to be crucial for membranous skeleton and embryonic development; however, little is known regarding the role of TMOD3 in liver cancer progressi...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.7052

    authors: Jin C,Chen Z,Shi W,Lian Q

    更新日期:2019-05-01 00:00:00

  • Expression of transglutaminases in human breast cancer and their possible clinical significance.

    abstract::Implicated in several physiologic processes, including tumour-host, some transglutaminases (TGase) have been noted to play a regulatory role in the extracellular matrix in cell adhesion and migration of cancer cells. This study sought to determine the level of expression of TGases and their possible clinical significa...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Jiang WG,Ablin R,Douglas-Jones A,Mansel RE

    更新日期:2003-11-01 00:00:00

  • BMI-1 suppression increases the radiosensitivity of oesophageal carcinoma via the PI3K/Akt signaling pathway.

    abstract::B-cell‑specific Moloney murine leukaemia virus integration site-1 (BMI-1) contributes to the growth of tumour cells post-irradiation (IR). The aim of the present study was to characterize the effects of BMI-1 on cell viability, radiosensitivity and its mechanisms of action in oesophageal squamous cell cancer (ESCC). W...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.6136

    authors: Yang XX,Ma M,Sang MX,Zhang XY,Liu ZK,Song H,Zhu SC

    更新日期:2018-02-01 00:00:00

  • Frizzled2 mediates the migration and invasion of human oral squamous cell carcinoma cells through the regulation of the signal transducer and activator of transcription-3 signaling pathway.

    abstract::Frizzled2 (Fzd2) is a receptor for wingless-type MMTV integration site family members (Wnts), the aberrant overexpression of which has been noted to contribute to cancer metastasis. The present study was performed to characterize the role of Fzd2 in the migration and invasion of oral squamous cell carcinomas (OSCC) in...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4285

    authors: Zhang E,Li Z,Xu Z,Duan W,Sun C,Lu L

    更新日期:2015-12-01 00:00:00

  • DHL‑TauZnNa, a newly synthesized α-lipoic acid derivative, induces autophagy in human colorectal cancer cells.

    abstract::In recent years, several antioxidant substances have been found to have an antiproliferative effect on various types of carcinomas. α-lipoic acid (ALA) induces apoptosis in several types of cancer cell lines, but it is difficult to apply α-lipoic acid in clinical use as it is easily oxidized and unstable. Recently, we...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2394

    authors: Hiratsuka T,Inomata M,Kono Y,Yokoyama S,Shiraishi N,Kitano S

    更新日期:2013-06-01 00:00:00

  • Changes in MYCN expression in human neuroblastoma cell lines following cisplatin treatment may not be related to MYCN copy numbers.

    abstract::Neuroblastoma is a tumor accounting for approximately 10% of all childhood malignancies and 50% of all childhood cancer-related deaths. MYCN gene copy number variation represents the most important prognostic factor in neuroblastoma. Prognostic significance of MYCN gene expression is more complicated and may depend on...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2383

    authors: Prochazka P,Hrabeta J,Vicha A,Cipro S,Stejskalova E,Musil Z,Vodicka P,Eckschlager T

    更新日期:2013-06-01 00:00:00

  • Inhibition of cell motility and invasion by HangAmDan-B in NCI-H460 human non-small cell lung cancer cells.

    abstract::Correlation between inhibition of cell motility and anti-invasive activity by the water extract of HangAmDan-B (HAD-B), a crude extract of eight Korean medicinal animals and plants, in NCI-H460 human non-small cell lung cancer (NSCLC) cells was investigated. Within the concentration...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1440

    authors: Choi YJ,Shin DY,Lee YW,Cho CK,Kim GY,Kim WJ,Yoo HS,Choi YH

    更新日期:2011-12-01 00:00:00

  • Artificial intelligence for predicting recurrence-free probability of non-invasive high-grade urothelial bladder cell carcinoma.

    abstract::The objective of our study was to define a neural network for predicting recurrence and progression-free probability in patients affected by recurrent pTaG3 urothelial bladder cancer to use in everyday clinical practice. Among all patients who had undergone transurethral resection for bladder tumors, 143 were finally ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Cai T,Conti G,Nesi G,Lorenzini M,Mondaini N,Bartoletti R

    更新日期:2007-10-01 00:00:00

  • Modulation of intestinal environment by prebiotic germinated barley foodstuff prevents chemo-induced colonic carcinogenesis in rats.

    abstract::Butyrate was shown to have a preventive effect on colon cancer in vivo. Germinated barley foodstuff (GBF) was in a prebiotic stage and had the potency to attenuate mucosal inflammation and to increase fecal butyrate production in colitis. This study aimed to determine whether the GBF treatment in a colon cancer model ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Kanauchi O,Mitsuyama K,Andoh A,Iwanaga T

    更新日期:2008-10-01 00:00:00

  • Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models of melanoma and breast cancer.

    abstract::Tumor invasion, angiogenesis and metastasis involve secretion of proteolytic enzymes and cell migration into blood vessels. Tumor cells are capable of degrading the extracellular matrix via a proteolytic cascade that includes urokinase-type plasminogen activator (uPA) and matrix metalloproteases (MMPs). We have invest...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Farina HG,Pomies M,Alonso DF,Gomez DE

    更新日期:2006-10-01 00:00:00

  • Combined analysis of gene expression, miRNA expression and DNA methylation profiles of osteosarcoma.

    abstract::Osteosarcoma (OS) is a common primary malignancy in children and adolescents with relative high survival rate after chemotherapy. While the toxicity of chemotherapy and personalized different response to chemotherapy makes it difficult for the selection of therapeutics and improvement of diagnosis. In this study, we c...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5324

    authors: Zhang W,Han S,Sun K

    更新日期:2017-02-01 00:00:00

  • miR‑107‑5p promotes tumor proliferation and invasion by targeting estrogen receptor‑α in endometrial carcinoma.

    abstract::The aberrant expression of miR107‑5p is closely related to the development of several types of human cancers. However, the role of miR‑107‑5p in endometrial carcinoma (EC) has not been fully confirmed. In the present study, we aimed to explore the function of miR‑107‑5p in EC carcinogenesis. EC samples and normal endo...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6936

    authors: Bao W,Zhang Y,Li S,Fan Q,Qiu M,Wang Y,Li Y,Ji X,Yang Y,Sang Z,Xu W,Yang Y,Wu S,Zhu Y

    更新日期:2019-03-01 00:00:00

  • Expression of CXCL12 and CXCR4 in pT3-stage gastric cancer does not correlate with peritoneal metastasis.

    abstract::CXCR4, a chemokine receptor, is considered to be involved in the metastastic formation of various types of cancer and could influence survival. More recently, CXCR4 was reported to be associated with peritoneal metastasis in gastric cancer, and CXCL12, its ligand, as a prognostic determinant among gastric cancer of va...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Tsuboi K,Kodera Y,Nakanishi H,Ito S,Mochizuki Y,Nakayama G,Koike M,Fujiwara M,Yamamura Y,Nakao A

    更新日期:2008-11-01 00:00:00