Antitumor activity of noscapine in human non-small cell lung cancer xenograft model

Jackson, Tanise; Chougule, Mahavir B.; Ichite, Nkechi; Patlolla, Ram R.; Singh, Mandip

doi:10.1007/s00280-008-0720-z

Cited by 88 publications

(98 citation statements)

References 25 publications

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“…The ratio of Bax/ Bcl-2 is a critical determinant of whether cells will undergo apoptosis. [41][42][43] In the present study, Ke increased pro-apoptotic Bax expression and decreased anti-apoptotic Bcl-2 expression, leading to an increased Bax/Bcl-2 ratio, which may be one of the molecular mechanisms by which Ke induces apoptosis.…”

Section: Discussionsupporting

confidence: 52%

A Novel Herbal Formula Induces Cell Cycle Arrest and Apoptosis in Association With Suppressing the PI3K/AKT Pathway in Human Lung Cancer A549 Cells

et al. 2013

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Aim of the study. In recent years, the incidence of lung cancer, as well as the mortality rate from this disease, has increased. Moreover, because of acquired drug resistance and adverse side effects, the effectiveness of current therapeutics used for the treatment of lung cancer has decreased significantly. Chinese medicine has been shown to have significant antitumor effects and is increasingly being used for the treatment of cancer. However, as the mechanisms of action for many Chinese medicines are undefined, the application of Chinese medicine for the treatment of cancer is limited. The formula tested has been used clinically by the China National Traditional Chinese Medicine Master, Professor Zhonging Zhou for treatment of cancer. In this article, we examine the efficacy of Ke formula in the treatment of non-small cell lung cancer and elucidate its mechanism of action. Methods. A Balb/c nude mouse xenograft model using A549 cells was previously established. The mice were randomly divided into normal, mock, Ke, cisplatin (DDP), and co-formulated (Ke + DDP) groups. After 15 days of drug administration, the animals were sacrificed, body weight and tumor volume were recorded, and the tumor-inhibiting rate was calculated. A cancer pathway finder polymerase chain reaction array was used to monitor the expression of 88 genes in tumor tissue samples. The potential antiproliferation mechanism was also investigated by Western blot analysis. Results. Ke formula minimized chemotherapy-related weight loss in tumor-bearing mice without exhibiting distinct toxicity. Ke formula also inhibited tumor growth, which was associated with the downregulation of genes in the PI3K/AKT, MAPK, and WNT/β-catenin pathways. The results from Western blot analyses further indicated that Ke blocked the cell cycle progression at the G1/S phase and induced apoptosis mainly via the PI3K/AKT pathway. Conclusion. Ke formula inhibits tumor growth in an A549 xenograft mouse model with no obvious side effects. Moreover, Ke exhibits synergistic antitumor effects when combined with DDP. The mechanism of action of Ke is to induce cell cycle arrest and apoptosis by suppressing the PI3K/AKT pathway. Further research will be required to determine the mechanism of action behind the synergistic effect of Ke and DDP.

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Section: Discussionsupporting

confidence: 52%

A Novel Herbal Formula Induces Cell Cycle Arrest and Apoptosis in Association With Suppressing the PI3K/AKT Pathway in Human Lung Cancer A549 Cells

et al. 2013

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“…Noscapine has been studied extensively in cancer research due to its effects on microtubule dynamics, and its antitumor activity has been demonstrated in multiple in vivo studies (25)(26)(27)(28). Our study demonstrates for the first time that (i) noscapine attenuates fibrotic responses both in cultured human pulmonary fibroblasts and in an experimental model of pulmonary fibrosis; (ii) noscapine activates PKA specifically in pulmonary fibroblasts but not in bronchial or alveolar epithelial cells; (iii) PKA activation mediates the antifibrotic effects of noscapine; and (iv) the mechanism of PKA stimulation by noscapine involves activation of EP 2 prostanoid receptors, which mediate regulation of myofibroblast differentiation by noscapine.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, studies by Joshi's group have shown that noscapine binds to tubulin, changes its conformation, and arrests dividing mammalian cells in mitosis through its effects on microtubule assembly (25). Therefore, noscapine has been studied extensively in cancer research, and its antitumor activity has been demonstrated in multiple in vivo studies (25)(26)(27)(28).…”

mentioning

confidence: 99%

Antifibrotic Effects of Noscapine through Activation of Prostaglandin E2 Receptors and Protein Kinase A

Kach

Sandbo

et al. 2014

Journal of Biological Chemistry

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Background: Noscapine is a safe orally available anticough medicine also known to bind microtubules and induce cancer cell death. Results: Noscapine inhibits myofibroblast differentiation and pulmonary fibrosis through prostaglandin receptors and activation of PKA. Conclusion: Noscapine is an antifibrotic drug acting through PKA activation via EP 2 prostaglandin receptors. Significance: This study describes a novel antifibrotic function and novel mechanism of action of noscapine.

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“…Biochemical markers are indicators for diagnosis and prognosis of malignant diseases [12]. The results of liver marker enzymes in DLA-bearing mice are depicted in Table 2.…”

Section: Biochemical Parametersmentioning

confidence: 99%

Antitumor Potential of Hydroethanolic Extract of Annona Muricata Leaves Against Dalton’s Lymphoma Ascites-Induced Tumor in Mice

Nalini¹,

Durairaj²

2018

Asian J Pharm Clin Res

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Objective: The objective of this study was to assess the antitumor activity of hydroethanolic extract of Annona muricata (HEEAM) in Dalton's lymphoma ascites (DLA)-induced tumor model. Methods:Antitumor activity of HEEAM was evaluated against DLA-induced tumor mice by assessing the antitumor, hematological, and biochemical parameters. Results:The results revealed that antitumor activity of HEEAM was observed in Swiss albino mice at the doses of 200 and 400 mg/kg body weight given orally for 15 days. The results indicated that administration of the extracts not only increased the survival of animals and decreased the body weight with ascites tumor but also altered many hematological and biochemical parameters. Both extracts exhibited a significant (p<0.05) antitumor activity on dose-dependent manner. Among the two doses, 400 mg/kg of HEEAM dose showed potent anticancer activity. Conclusion:The findings confirmed that the HEEAM possess potent antitumor activity, and hence, it might be used as a natural anticancer agent.

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Antitumor activity of noscapine in human non-small cell lung cancer xenograft model

Cited by 88 publications

References 25 publications

A Novel Herbal Formula Induces Cell Cycle Arrest and Apoptosis in Association With Suppressing the PI3K/AKT Pathway in Human Lung Cancer A549 Cells

A Novel Herbal Formula Induces Cell Cycle Arrest and Apoptosis in Association With Suppressing the PI3K/AKT Pathway in Human Lung Cancer A549 Cells

Antifibrotic Effects of Noscapine through Activation of Prostaglandin E2 Receptors and Protein Kinase A

Antitumor Potential of Hydroethanolic Extract of Annona Muricata Leaves Against Dalton’s Lymphoma Ascites-Induced Tumor in Mice

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