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Gigantol Suppresses Cancer Stem Cell-Like Phenotypes in Lung Cancer Cells
Narumol Bhummaphan1, Pithi Chanvorachote2
1Cell-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.
Insights
Gigantol, a compound from Dendrobium draconis, effectively suppresses cancer stem cell (CSC) properties in lung cancer. This compound reduces tumor growth and key CSC markers, offering therapeutic potential.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Cancer stem cells (CSCs) drive tumor malignancy, metastasis, and relapse.
- Targeting CSCs is a key strategy in cancer research and drug development.
- Identifying novel compounds that inhibit CSCs is of significant interest.
Purpose of the Study:
- To investigate the potential of gigantol, a compound from Dendrobium draconis, in suppressing cancer stem cell phenotypes.
- To evaluate the effects of gigantol on the stem-like properties of human lung cancer cells.
Main Methods:
- Treatment of human lung cancer cells with gigantol at nontoxic concentrations.
- Assessment of anchorage-independent growth and survival.
- Evaluation of tumor spheroid formation capacity.
- Analysis of cancer stem cell markers (CD133, ALDH1A1).
- Investigation of the underlying molecular mechanisms involving the Akt signaling pathway and pluripotency factors (Oct4, Nanog).
Main Results:
- Gigantol significantly suppressed stem-like phenotypes in human lung cancer cells.
- Nontoxic concentrations of gigantol reduced anchorage-independent growth and survival.
- Gigantol markedly decreased tumor spheroid formation, a critical CSC hallmark.
- Treatment with gigantol led to reduced expression of lung CSC markers CD133 and ALDH1A1.
- Gigantol suppressed Akt signaling, decreasing cellular levels of Oct4 and Nanog, thereby reducing stemness.
Conclusions:
- Gigantol exhibits significant cancer stem cell-suppressing activity in lung cancer.
- The mechanism involves the suppression of Akt signaling and downstream pluripotency factors.
- Gigantol shows therapeutic potential for targeting CSCs in cancer treatment strategies.
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