Naturally occurring products in cancer therapy

Rajesh, E.; Sankari, S. Leena; Malathi, L.; Krupaa, Jayasri

doi:10.4103/0975-7406.155895

Cited by 111 publications

(79 citation statements)

References 28 publications

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“…Natural substances from plant sources, including vanillin, have gained increased interest in an alternative therapy due to their various pharmacological activities (20). Vanillin, 4-hydroxy-3-methoxybenzaldehyde ( Fig.…”

Section: Suppression Of Cancer Stem-like Phenotypes In Nci-h460 Lung mentioning

confidence: 99%

Suppression of cancer stem-like phenotypes in NCI-H460 lung cancer cells by vanillin through an Akt-dependent pathway

Srinual

Chanvorachote

Pongrakhananon

2017

International Journal of Oncology

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Abstract. Cancer stem cells (CSCs) have been reported as a major cause of cancer metastasis and the failure of cancer treatment. Cumulative studies have indicated that protein kinase B (Akt) and its downstream signaling pathway, including CSC markers, play a critical role in the aggressive behavior of this cancer. In this study, we investigated whether vanillin, a major component in Vanilla planifolia seed, could suppress cancer stemness phenotypes and related proteins in the human non-small cell lung cancer NCI-H460 cell line. A non-toxic concentration of vanillin suppressed spheroid and colony formation, two hallmarks of the cancer stemness phenotype, in vitro in NCI-H460 cells. Western blot analysis revealed that the CSC markers CD133 and ALDH1A1 and the associated transcription factors, Oct4 and Nanog, were extensively downregulated by vanillin. Vanillin also attenuated the expression and activity of Akt, a transcription regulator upstream of CSCs, an action that was confirmed by treatment with the Akt inhibitor perifosine. Furthermore, the ubiquitination of Akt was elevated in response to vanillin treatment prior to proteasomal degradation. This finding indicates that vanillin can inhibit cancer stem cell-like behavior in NCI-H460 cells through the induction of Akt-proteasomal degradation and reduction of downstream CSC transcription factors. This inhibitory effect of vanillin may be an alternative approach in the treatment against lung cancer metastasis and its resistance to chemotherapy. IntroductionLung cancer has been reported as a major cause of mortality with a high metastasis rate compared with other types of cancers (1). Lung cancer cells contain a small population called tumor-initiating cells or cancer stem cells (CSCs) that have extremely tumorigenic, self-renewal and differentiating properties, resulting in a prolonged tumor status, resistance to chemotherapy and cancer relapse (2,3). Clinical observation has reported that this CSC subpopulation is found in cancer specimens and remains an obstacle for cancer treatment (4). In vitro and in vivo studies have revealed that lung cancer stem cells are extensively resistant to the first-line therapy cisplatin compared with neighboring cancer cells (5,6). These CSCs can maintain the cell survival signaling that provides their strength under severe environments (7). Therefore, the attenuation or removal of CSCs would be likely to improve patient outcome.Like other types of stem cells, CSCs express specific surface markers, including octamer-binding transcription factor 4 (Oct4), Nanog, ATP-binding cassette subfamily G member 2 (ABCG2), and CD133. Oct4 and Nanog are transcription factors that are responsible for maintaining pluripotency, self-renewal proliferation and tumorigenicity in both normal stem cells and cancer stem cells (8,9). Several studies have reported that an elevation of Oct4 and Nanog is tightly related to a low survival rate and high incidence of cancer metastases (10,11). In lung cancer, both Oct4 and Nanog are required to maintain the...

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Section: Suppression Of Cancer Stem-like Phenotypes In Nci-h460 Lung mentioning

confidence: 99%

Suppression of cancer stem-like phenotypes in NCI-H460 lung cancer cells by vanillin through an Akt-dependent pathway

Srinual

Chanvorachote

Pongrakhananon

2017

International Journal of Oncology

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“…2 Many studies with plant extracts revealed that some of these plants had anti-tumor activity, thus being a source of compounds for successful development of anticancer drugs. 3,4 One example is paclitaxel (Taxol), derived from Taxus brevifolia (from the family Taxaceae) and currently clinically used in the treatment of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Melissa officinalisL. ethanolic extract inhibits the growth of a lung cancer cell line by interfering with the cell cycle and inducing apoptosis

et al. 2018

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Melissa officinalis is a plant from the family Lamiaceae, native in Europe particularly in the Mediterranean region. Given our interest in identifying extracts and compounds capable of inhibiting tumor cell growth, and given the antioxidant content and the high consumption of Melissa officinalis in Portugal, this study aimed to test the tumor cell growth inhibitory activity of five different extracts of this plant (aqueous, methanolic, ethanolic, hydromethanolic and hydroethanolic) in three human tumor cell lines: MCF-7, AGS and NCI-H460. All extracts decreased cell growth in all cell lines in a concentration-dependent manner. The ethanolic extract was the most potent one, presenting a GI 50 concentration of approximately 100.9 µg mL −1 in the NCI-H460 lung cancer cells. This extract was characterized by LC-DAD-ESI/MS regarding its phenolic composition, revealing rosmarinic acid as the most abundant compound. The GI 75 concentration of this extract affected the cell cycle profile of these cells. In addition, both the GI 50 and the GI 75 concentrations of the extract induced cellular apoptosis. Moreover, treatment of NCI-H460 cells with this extract caused a decrease in pro-caspase 3 and an increase in p53 levels. This study emphasizes the relevance of the study of natural products as inhibitors of tumor cell growth.

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“…Whereas single synthetic molecules were favored for targeted therapies in the past, they have been associated with shortcomings including toxicity, high cost, and drug resistance phenotypes [14,15]. Natural home medicine ingredients have been shown to provide a safer and holistic remedies for treatment of stress and cancer and are often predicted to offer additional benefits such as higher and broad spectrum efficacy [16,17].…”

Section: Introductionmentioning

confidence: 99%

Anti-Stress and Glial Differentiation Effects of a Novel Combination of Cucurbitacin B and Withanone (CucWi-N): Experimental Evidence

2018

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Background: Natural extracts and compounds used in traditional home medicine are known for their safety and a variety of health promoting and therapeutic potentials. In contrast to the single molecule mediated targets, the combinational therapies are preferred for their multi-functional and limited toxic regimens and may be useful for disease therapeutics as well as to increase the quality of life during a variety of environmental stresses. Purpose: We aimed to combine the active ingredients of Chinese (Helicteres angustifolia) and Indian (Withania somnifera) ginsengs to develop a natural, efficient, and welfare combinatorial mixture with high anti-stress and glial differentiation potentials. Methods: Using cultured cells as a model system, we developed a combination of active ingredients of Chinese (Cucurbitacin B [Cuc]) and Indian (Withanone [Wi-N]) ginsengs. Eleven chemical models of environmental stresses were used. Cytotoxicity studies were performed using human skin fibroblast for anti-stress and rat glioma cells for glial differentiation effects. Results: We demonstrate that the novel combination of Cuc and Wi-N, CucWi-N, was non-toxic to normal cells. It caused stress protection in assays using normal human fibroblasts subjected to a variety of stresses. Of note, cells showed remarkable protection against oxidative and UV stresses and marked by decrease in DNA damage and reactive oxygen species. We examined and found the glial differentiation potential of CucWi-N in rat glioblastoma cells. CucWi-N clearly induced differentiation phenotype, well-marked with upregulation of GAP43, MAP2, and GFAP, which have been shown to play a key role in glial differentiation. Conclusion: These data demonstrate anti-stress and glial differentiation potential of CucWi-N (a novel combination of Cuc and Wi-N) that could be recruited in nutraceutical and pharmaceutical avenues and hence warrant further evaluation and mechanistic studies.

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Naturally occurring products in cancer therapy

Cited by 111 publications

References 28 publications

Suppression of cancer stem-like phenotypes in NCI-H460 lung cancer cells by vanillin through an Akt-dependent pathway

Suppression of cancer stem-like phenotypes in NCI-H460 lung cancer cells by vanillin through an Akt-dependent pathway

Melissa officinalisL. ethanolic extract inhibits the growth of a lung cancer cell line by interfering with the cell cycle and inducing apoptosis

Anti-Stress and Glial Differentiation Effects of a Novel Combination of Cucurbitacin B and Withanone (CucWi-N): Experimental Evidence

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