α-Chaconine-reduced Metastasis Involves a PI3K/Akt Signaling Pathway with Downregulation of NF-κB in Human Lung Adenocarcinoma A549 cells

Shih, Yuan-Wei; Chen, Pin-Shern; Wu, Cheng‐Hsun; Jeng, Ya-Fang; Wang, Chau‐Jong

doi:10.1021/jf072423r

Cited by 74 publications

(50 citation statements)

References 25 publications

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“…Existing data indicate that the MAPK pathway is related to paclitaxel-or K8-induced cell death in three different human cancer cell lines: HeLa cervical carcinoma, MCF7 breast cancer, and A431 squamous carcinoma cells (Bacus et al, 2001). The mitogen-induced ERK MAPKs are linked to cell proliferation and survival, whereas the stress-activated MAPKs, p38, and JNK are involved in apoptosis (Wang et al, 2004;Shih et al, 2007). Here, we found that paclitaxel or K8 alone induced ERK activation, whereas the combination of these two compounds synergistically induced activation of ERK (Fig.…”

Section: Discussionmentioning

confidence: 99%

Synergistic anti‐tumor activity of isochaihulactone and paclitaxel on human lung cancer cells

Chen

et al. 2011

Journal Cellular Physiology

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Drug resistance frequently develops in tumors during chemotherapy. Therefore, to improve the clinical outcome, more effective and tolerable combination treatment strategies are needed. Here, we show that isochaihulactone (K8) enhanced paclitaxel-induced apoptotic death in human lung cancer cells, and the enhancing effect was related to increased NSAID-activated gene-1 (NAG-1) expression. CalcuSyn software was used to evaluate the synergistic interaction of K8 and paclitaxel on human lung cancer cells; the synergistic effect of K8 in combination with paclitaxel was increased more than either of these drugs alone. Furthermore, the activity of ERK1/2 was enhanced by the combination of K8 and paclitaxel, and an ERK1/2 inhibitor dramatically inhibited NAG-1 expression in human lung cancer cells. Therefore, this synergistic apoptotic effect in human lung cancer cells may be directly associated with K8-induced NAG-1 expression through ERK1/2 activation. Moreover, over-expression of NAG-1 enhanced K8/paclitaxel-induced apoptosis in human lung cancer cells. In addition, treatment of nude mice with K8 combined with paclitaxel induced phospho-ERK1/2 and NAG-1 expression in vivo. Targeting of NAG-1 signaling could enhance therapeutic efficacy in lung cancer. Our results reveal that activation of NAG-1 by K8 enhanced the therapeutic efficacy of paclitaxel in human lung cancer cells via the ERK1/2 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Synergistic anti‐tumor activity of isochaihulactone and paclitaxel on human lung cancer cells

Chen

et al. 2011

Journal Cellular Physiology

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“…Seo et al [114] reported that tangeretin inhibited platelet-derived growth factor-(PGDF-) BB-induced proliferation and migration of aortic smooth muscle cells by blocking AKT activation in a dose-dependent manner. The existing study indicated that the FAK/PI3K/Akt is involved in the regulation of MMP-2 and MMP-9 activities on different cell types [115]. In addition, NF-κB has been known to translocate to the nucleus and regulate the expressions of multiple genes involved in MMP-2/MMP-9 secretions.…”

Section: Anti-metastasismentioning

confidence: 99%

<i>Citrus</i> Flavonoids and Human Cancers

Ke¹,

Pan²,

Xu³

et al. 2015

JFNR

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Nowadays cancers pose a great threat to the health of human beings. Based on studies on the flavonoids and other bioactive compounds of Citrus fruits in current literature, it was widely suggested that the consumption of Citrus fruits is beneficial to the prevention and treatment of human chronic diseases including cancers. In the past decades, the study concerning Citrus flavonoids has covered various areas including the type, content and distribution of flavonoids in fruits; their variation between wild and cultivated genotypes; their antioxidant, antiinflammation, anti-aging, antimicrobial and anticarcinogenic activities. To enlighten future Citrus germplasm study, this review introduces briefly the functions of main types of Citrus flavonoids, including antioxidant, antiinflammation and anti-aging activities, and their relationships to human cancers. Most importantly, the mechanisms of action by which Citrus flavonoids play their roles in human cancer prevention and treatment were summarized.

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“…In our previous report, we found that a-chaconine inhibited A549 cell metastasis by a reduction of MMP-2 and MMP-9 activities involving suppression of JNK and the PI3K/Akt/NF-kB signaling pathway. 33) a-Chaconine and a-solanine are major glycoalkaloids in potato and differ only in the nature of the carbohydrate side chain attached to the 3-OH group of solanidine. Thus, we suggested that these two structural similar compounds possess similar antimetastatic potential.…”

Section: )mentioning

confidence: 99%

.ALPHA.-Solanine Inhibits Human Melanoma Cell Migration and Invasion by Reducing Matrix Metalloproteinase-2/9 Activities

Shih

Chien

et al. 2010

Biological & Pharmaceutical Bulletin

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Glycoalkaloids are the biologically active secondary metabolites found in many plants, such as potatoes. Glycoalkaloids are produced in leaves, roots, tubers and sprouts of the potato plant, and are involved in host plant resistance to bacteria, fungi, viruses, and insects.1) Several reports have showed that glycoalkaloids suppress the growth of cancer cells in human skin, liver, prostate, breast and colon.2-4) aSolanine, a trisaccharide glycoalkaloid, is one of the main steroidal glycoalkaloids in potatoes (Solanum tuberosum). 1)Recent studies have demonstrated that a-solanine inhibits the growth of human colon (HT29), liver (HepG2), cervical (HeLa), lymphoma (U937), and stomach (AGS and KATO III) cancer cells.3,5) a-Solanine has also been shown to induce apoptosis of human colon cancer cells through the inhibition of extracellular signal regulating kinase (ERK) phosphorylation and activation of caspase-3.6) Therefore, a-solanine may possess the potential for cancer chemotherapeutic action.Melanoma is a skin cancer that arises from the transformation of melanocytes, which are normally found in the basal layer of the epidermis. Melanoma accounts for nearly 4% of skin cancer cases but for 74% of all skin cancer mortalities. 7)Melanoma development and progression have been welldescribed as a sequential process. Following transformation of melanocytes, tumors undergo horizontal or radial initial growth phase followed by a subsequent vertical growth phase, in which melanoma cells infiltrate and invade the dermis and exhibit metastatic potential. 8,9) The conversion of benign to malignant melanoma is characterized by genetic alteration and frequent chromosomal abnormalities.10,11) Therefore, malignant melanoma has served as an excellent model for investigating the molecular changes associated with the metastatic phenotype.Cancer metastasis is a highly coordinated multistep process, in which cancer cells degrade the extracellular matrix (ECM), penetrate through the basement membrane of capillary and lymphatic vessels, intravasate, and then invade and grow in new tissue.12) The process of metastasis is promoted by expressing and secreting various proteolytic enzymes that can degrade most ECM components. Matrix metalloproteinases (MMPs), a family of Zn-dependent endopeptidases, are the major proteases participating in tumor cell migration, spreading, tissue invasion and metastasis.13) Several MMPs, such as MMP-2 and MMP-9, contribute to the process of metastasis.14,15) The activation of these enzymes enables the degradation of ECM by cancer cells, allowing their access to the vasculature, as well as their migration, and invasion into the target organ and development of cancer metastasis. 13)In addition to MMPs, the mitogen-activated protein kinase family members (MAPK) are also known to mediate metastasis. MAPK family members participate in numerous signaling cascades that play important regulatory roles in cell growth, apoptosis, differentiation, and metastasis. 16,17) The diverse MAPK members are activated in response...

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α-Chaconine-reduced Metastasis Involves a PI3K/Akt Signaling Pathway with Downregulation of NF-κB in Human Lung Adenocarcinoma A549 cells

Cited by 74 publications

References 25 publications

Synergistic anti‐tumor activity of isochaihulactone and paclitaxel on human lung cancer cells

Synergistic anti‐tumor activity of isochaihulactone and paclitaxel on human lung cancer cells

<i>Citrus</i> Flavonoids and Human Cancers

.ALPHA.-Solanine Inhibits Human Melanoma Cell Migration and Invasion by Reducing Matrix Metalloproteinase-2/9 Activities

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