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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

Akt inhibitor perifosine suppresses CD133, Oct4, and Nanog. (a) H460 cells were treated with perifosine (0–10 µM) for 48 h. Cells were collected and CSCs marker CD133 and the cellular levels of self-renewal pluripotency transcription factors, Oct4 and Nanog, were analyzed by Western blotting. The blots were reprobed with α-tubulin to confirm equal loading. (b) Signals were quantified by densitometry, and mean data from independent experiments were normalized to the controls. The bars are means ± SD (n = 3). ∗P < 0.05 versus nontreated cells.
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fig6: Akt inhibitor perifosine suppresses CD133, Oct4, and Nanog. (a) H460 cells were treated with perifosine (0–10 µM) for 48 h. Cells were collected and CSCs marker CD133 and the cellular levels of self-renewal pluripotency transcription factors, Oct4 and Nanog, were analyzed by Western blotting. The blots were reprobed with α-tubulin to confirm equal loading. (b) Signals were quantified by densitometry, and mean data from independent experiments were normalized to the controls. The bars are means ± SD (n = 3). ∗P < 0.05 versus nontreated cells.

Mentions: The activity of phosphorylated Akt has been shown to link with the proliferation and self-renewal properties of normal and cancer stem cells [12, 24, 32–35]. Evidence has suggested that Akt activity resulted in the increase of cellular levels of self-renewal pluripotency transcription factor Oct4 and Nanog [25, 36, 37]. We further tested whether gigantol suppressed the CSCs through such a pathway. Cells were treated with the nontoxic concentrations of gigantol for 48 h, and phosphorylated Akt, total Akt, Oct4, and Nanog were determined by Western blotting. Figure 5 shows that the treatment of the cells with gigantol caused decrease of phosphorylated Akt in a dose-dependent manner, whereas total Akt was not altered in comparison to those of nontreated control. Also, its downstream transcription factors including Oct4 and Nanog were found to be significantly reduced following the reduction of phosphorylated Akt. Previous study showed that perifosine (known as Akt inhibitor) reduced the number of mammospheres [38]. To confirm that gigantol regulates Nanog and Oct4 mediated by Akt-dependent mechanism, we used perifosine to study. H460 cells were treated with noncytotoxic concentrations of perifosine (0–10 µM) for 48 h, and the stem cell-regulating proteins were analyzed using Western blot analysis. Figure 6 shows that treatment of the cells with perifosine significantly reduced phosphorylated Akt with only minimal change of total Akt. Importantly, such an Akt inhibitor significantly suppressed CD133 expression in a dose-dependent manner. Also, the downstream transcription factors including Oct4 and Nanog were found to decrease as a consequence of phosphorylated Akt reduction. Therefore, our results have demonstrated that gigantol possesses the CSCs reducing effect and could be beneficial for the treatment of lung cancer by targeting CSCs.


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

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

Akt inhibitor perifosine suppresses CD133, Oct4, and Nanog. (a) H460 cells were treated with perifosine (0–10 µM) for 48 h. Cells were collected and CSCs marker CD133 and the cellular levels of self-renewal pluripotency transcription factors, Oct4 and Nanog, were analyzed by Western blotting. The blots were reprobed with α-tubulin to confirm equal loading. (b) Signals were quantified by densitometry, and mean data from independent experiments were normalized to the controls. The bars are means ± SD (n = 3). ∗P < 0.05 versus nontreated cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig6: Akt inhibitor perifosine suppresses CD133, Oct4, and Nanog. (a) H460 cells were treated with perifosine (0–10 µM) for 48 h. Cells were collected and CSCs marker CD133 and the cellular levels of self-renewal pluripotency transcription factors, Oct4 and Nanog, were analyzed by Western blotting. The blots were reprobed with α-tubulin to confirm equal loading. (b) Signals were quantified by densitometry, and mean data from independent experiments were normalized to the controls. The bars are means ± SD (n = 3). ∗P < 0.05 versus nontreated cells.
Mentions: The activity of phosphorylated Akt has been shown to link with the proliferation and self-renewal properties of normal and cancer stem cells [12, 24, 32–35]. Evidence has suggested that Akt activity resulted in the increase of cellular levels of self-renewal pluripotency transcription factor Oct4 and Nanog [25, 36, 37]. We further tested whether gigantol suppressed the CSCs through such a pathway. Cells were treated with the nontoxic concentrations of gigantol for 48 h, and phosphorylated Akt, total Akt, Oct4, and Nanog were determined by Western blotting. Figure 5 shows that the treatment of the cells with gigantol caused decrease of phosphorylated Akt in a dose-dependent manner, whereas total Akt was not altered in comparison to those of nontreated control. Also, its downstream transcription factors including Oct4 and Nanog were found to be significantly reduced following the reduction of phosphorylated Akt. Previous study showed that perifosine (known as Akt inhibitor) reduced the number of mammospheres [38]. To confirm that gigantol regulates Nanog and Oct4 mediated by Akt-dependent mechanism, we used perifosine to study. H460 cells were treated with noncytotoxic concentrations of perifosine (0–10 µM) for 48 h, and the stem cell-regulating proteins were analyzed using Western blot analysis. Figure 6 shows that treatment of the cells with perifosine significantly reduced phosphorylated Akt with only minimal change of total Akt. Importantly, such an Akt inhibitor significantly suppressed CD133 expression in a dose-dependent manner. Also, the downstream transcription factors including Oct4 and Nanog were found to decrease as a consequence of phosphorylated Akt reduction. Therefore, our results have demonstrated that gigantol possesses the CSCs reducing effect and could be beneficial for the treatment of lung cancer by targeting CSCs.

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