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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

Gigantol suppresses CSC-like phenotypes. (a) After being treated with gigantol (0–20 µM) for 48 h, H460 cells were suspended and subjected to spheroid formation assay. (b) 4x phase-contrast images of primary spheroids at day 7 were captured for treated and nontreated cells. (c) The primary spheroids were resuspended into single cells, and secondary spheroids were allowed to grow for 30 days. (d) 4x phase-contrast images of secondary spheroids at day 30 were presented. All plots are means ± SD (n = 3). ∗P < 0.05 versus nontreated cells.
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fig3: Gigantol suppresses CSC-like phenotypes. (a) After being treated with gigantol (0–20 µM) for 48 h, H460 cells were suspended and subjected to spheroid formation assay. (b) 4x phase-contrast images of primary spheroids at day 7 were captured for treated and nontreated cells. (c) The primary spheroids were resuspended into single cells, and secondary spheroids were allowed to grow for 30 days. (d) 4x phase-contrast images of secondary spheroids at day 30 were presented. All plots are means ± SD (n = 3). ∗P < 0.05 versus nontreated cells.

Mentions: To confirm the above effect of gigantol on CSCs, the lung cancer cells were similarly treated and subjected to the spheroid formation assay. Cells were pretreated with gigantol for 48 h, detached, resuspended, and seeded at low density onto ultralow attachment plates. The primary spheroids were allowed to form for 7 days (Figure 3(a)). The primary spheroids were then detached and resuspended. The secondary spheroids were allowed to grow for 30 days in RPMI serum-free medium (Figure 3(d)). In the nontreated control cells, the cells have an ability to form aggregates and spheroids in the primary detection. Although the number and size of spheroids were found to be significantly diminished in the secondary spheroids, there are a number of spheroids remaining in such a condition referring to the presence of CSCs in H460 populations. Interestingly, treatment of the cells with nontoxic concentrations of gigantol dramatically reduced both number and size of tumor spheroids (Figure 3), suggesting that the compound has a suppressing effect on the CSCs populations in these cells.


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

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

Gigantol suppresses CSC-like phenotypes. (a) After being treated with gigantol (0–20 µM) for 48 h, H460 cells were suspended and subjected to spheroid formation assay. (b) 4x phase-contrast images of primary spheroids at day 7 were captured for treated and nontreated cells. (c) The primary spheroids were resuspended into single cells, and secondary spheroids were allowed to grow for 30 days. (d) 4x phase-contrast images of secondary spheroids at day 30 were presented. 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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getmorefigures.php?uid=PMC4539074&req=5

fig3: Gigantol suppresses CSC-like phenotypes. (a) After being treated with gigantol (0–20 µM) for 48 h, H460 cells were suspended and subjected to spheroid formation assay. (b) 4x phase-contrast images of primary spheroids at day 7 were captured for treated and nontreated cells. (c) The primary spheroids were resuspended into single cells, and secondary spheroids were allowed to grow for 30 days. (d) 4x phase-contrast images of secondary spheroids at day 30 were presented. All plots are means ± SD (n = 3). ∗P < 0.05 versus nontreated cells.
Mentions: To confirm the above effect of gigantol on CSCs, the lung cancer cells were similarly treated and subjected to the spheroid formation assay. Cells were pretreated with gigantol for 48 h, detached, resuspended, and seeded at low density onto ultralow attachment plates. The primary spheroids were allowed to form for 7 days (Figure 3(a)). The primary spheroids were then detached and resuspended. The secondary spheroids were allowed to grow for 30 days in RPMI serum-free medium (Figure 3(d)). In the nontreated control cells, the cells have an ability to form aggregates and spheroids in the primary detection. Although the number and size of spheroids were found to be significantly diminished in the secondary spheroids, there are a number of spheroids remaining in such a condition referring to the presence of CSCs in H460 populations. Interestingly, treatment of the cells with nontoxic concentrations of gigantol dramatically reduced both number and size of tumor spheroids (Figure 3), suggesting that the compound has a suppressing effect on the CSCs populations in these cells.

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