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Gigantol Suppresses Cancer Stem Cell-Like Phenotypes in Lung Cancer Cells.

Bhummaphan N, Chanvorachote P - Evid Based Complement Alternat Med (2015)

Bottom Line: Importantly, gigantol significantly reduced the ability of the cancer cells to form tumor spheroids, a critical hallmark of CSCs.Concomitantly, the treatment of the compound was shown to reduce well-known lung CSCs markers, including CD133 and ALDH1A1.In conclusion, gigantol possesses CSCs suppressing activity which may facilitate the development of this compound for therapeutic approaches by targeting CSCs.

View Article: PubMed Central - PubMed

Affiliation: Cell-Based Drug and Health Product Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

ABSTRACT
As cancer stem cells (CSCs) contribute to malignancy, metastasis, and relapse of cancers, potential of compound in inhibition of CSCs has garnered most attention in the cancer research as well as drug development fields recently. Herein, we have demonstrated for the first time that gigantol, a pure compound isolated from Dendrobium draconis, dramatically suppressed stem-like phenotypes of human lung cancer cells. Gigantol at nontoxic concentrations significantly reduced anchorage-independent growth and survival of the cancer cells. Importantly, gigantol significantly reduced the ability of the cancer cells to form tumor spheroids, a critical hallmark of CSCs. Concomitantly, the treatment of the compound was shown to reduce well-known lung CSCs markers, including CD133 and ALDH1A1. Moreover, we revealed that gigantol decreased stemness in the cancer cells by suppressing the activation of protein kinase B (Akt) signal which in turn decreased the cellular levels of pluripotency and self-renewal factors Oct4 and Nanog. In conclusion, gigantol possesses CSCs suppressing activity which may facilitate the development of this compound for therapeutic approaches by targeting CSCs.

No MeSH data available.


Related in: MedlinePlus

Cytotoxic effect of gigantol on human lung cancer H460 cells. (a) H460 cells and (b) HaCaT cells were treated with various concentrations of gigantol (0–50 µM) for 24 and 48 h. Cell viability was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The viability of untreated cells was represented as 100%. ((c) and (d)) H460 cells were treated with gigantol (0–50 µM) for 48 h. Apoptotic and necrotic cell death were evaluated using Hoechst 33342/PI staining and calculated as a percentage compared with nontreated control cells. All plots are means ± SD (n = 3). ∗P < 0.05 versus nontreated cells.
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fig1: Cytotoxic effect of gigantol on human lung cancer H460 cells. (a) H460 cells and (b) HaCaT cells were treated with various concentrations of gigantol (0–50 µM) for 24 and 48 h. Cell viability was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The viability of untreated cells was represented as 100%. ((c) and (d)) H460 cells were treated with gigantol (0–50 µM) for 48 h. Apoptotic and necrotic cell death were evaluated using Hoechst 33342/PI staining and calculated as a percentage compared with nontreated control cells. All plots are means ± SD (n = 3). ∗P < 0.05 versus nontreated cells.

Mentions: Previous studies found that CSCs within tumors drive tumor growth and recurrence [2]. To test whether gigantol has an effect on CSCs phenotypes, we first characterized the noncytotoxic concentrations of the tested compound. Human lung cancer cells and normal keratinocyte stem cells were treated with various concentrations of gigantol (0, 1, 5, 10, 20, and 50 µM), and cell viability was determined after 24 and 48 h by MTT viability assay. Gigantol was considered nontoxic at the doses below 20 µM for both the lung cancer H460 and keratinocyte cells (Figures 1(a) and 1(b)). In addition, analysis of the mode of cell death (apoptosis and necrosis) using Hoechst33342/propidium iodide staining assay showed that treatment of the compound at 0–20 µM caused neither apoptosis nor necrosis to H460 cells. The significant increase of apoptosis was only found in the H460 cells treated with 50 µM gigantol (Figures 1(c) and 1(d)).


Gigantol Suppresses Cancer Stem Cell-Like Phenotypes in Lung Cancer Cells.

Bhummaphan N, Chanvorachote P - Evid Based Complement Alternat Med (2015)

Cytotoxic effect of gigantol on human lung cancer H460 cells. (a) H460 cells and (b) HaCaT cells were treated with various concentrations of gigantol (0–50 µM) for 24 and 48 h. Cell viability was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The viability of untreated cells was represented as 100%. ((c) and (d)) H460 cells were treated with gigantol (0–50 µM) for 48 h. Apoptotic and necrotic cell death were evaluated using Hoechst 33342/PI staining and calculated as a percentage compared with nontreated control cells. All plots are means ± SD (n = 3). ∗P < 0.05 versus nontreated cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig1: Cytotoxic effect of gigantol on human lung cancer H460 cells. (a) H460 cells and (b) HaCaT cells were treated with various concentrations of gigantol (0–50 µM) for 24 and 48 h. Cell viability was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The viability of untreated cells was represented as 100%. ((c) and (d)) H460 cells were treated with gigantol (0–50 µM) for 48 h. Apoptotic and necrotic cell death were evaluated using Hoechst 33342/PI staining and calculated as a percentage compared with nontreated control cells. All plots are means ± SD (n = 3). ∗P < 0.05 versus nontreated cells.
Mentions: Previous studies found that CSCs within tumors drive tumor growth and recurrence [2]. To test whether gigantol has an effect on CSCs phenotypes, we first characterized the noncytotoxic concentrations of the tested compound. Human lung cancer cells and normal keratinocyte stem cells were treated with various concentrations of gigantol (0, 1, 5, 10, 20, and 50 µM), and cell viability was determined after 24 and 48 h by MTT viability assay. Gigantol was considered nontoxic at the doses below 20 µM for both the lung cancer H460 and keratinocyte cells (Figures 1(a) and 1(b)). In addition, analysis of the mode of cell death (apoptosis and necrosis) using Hoechst33342/propidium iodide staining assay showed that treatment of the compound at 0–20 µM caused neither apoptosis nor necrosis to H460 cells. The significant increase of apoptosis was only found in the H460 cells treated with 50 µM gigantol (Figures 1(c) and 1(d)).

Bottom Line: Importantly, gigantol significantly reduced the ability of the cancer cells to form tumor spheroids, a critical hallmark of CSCs.Concomitantly, the treatment of the compound was shown to reduce well-known lung CSCs markers, including CD133 and ALDH1A1.In conclusion, gigantol possesses CSCs suppressing activity which may facilitate the development of this compound for therapeutic approaches by targeting CSCs.

View Article: PubMed Central - PubMed

Affiliation: Cell-Based Drug and Health Product Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

ABSTRACT
As cancer stem cells (CSCs) contribute to malignancy, metastasis, and relapse of cancers, potential of compound in inhibition of CSCs has garnered most attention in the cancer research as well as drug development fields recently. Herein, we have demonstrated for the first time that gigantol, a pure compound isolated from Dendrobium draconis, dramatically suppressed stem-like phenotypes of human lung cancer cells. Gigantol at nontoxic concentrations significantly reduced anchorage-independent growth and survival of the cancer cells. Importantly, gigantol significantly reduced the ability of the cancer cells to form tumor spheroids, a critical hallmark of CSCs. Concomitantly, the treatment of the compound was shown to reduce well-known lung CSCs markers, including CD133 and ALDH1A1. Moreover, we revealed that gigantol decreased stemness in the cancer cells by suppressing the activation of protein kinase B (Akt) signal which in turn decreased the cellular levels of pluripotency and self-renewal factors Oct4 and Nanog. In conclusion, gigantol possesses CSCs suppressing activity which may facilitate the development of this compound for therapeutic approaches by targeting CSCs.

No MeSH data available.


Related in: MedlinePlus