Cancer Stem Cell–Suppressing Activity of Chrysotoxine, a Bibenzyl from<i>Dendrobium pulchellum</i>

Bhummaphan, Narumol; Pongrakhananon, Varisa; Sritularak, Boonchoo; Chanvorachote, Pithi

doi:10.1124/jpet.117.244467

Cited by 27 publications

(25 citation statements)

References 47 publications

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“…Since these five compounds were diluted in dimethyl sulfoxide (DMSO), the same concentration of DMSO was added to the control culture without any compounds. We tested three known therapeutic concentrations [5][6][7][8][9], which were 5, 10 and 20 μM. After 2 hours of incubation, we stimulated monocytes by adding 100 ng/mL LPS and incubated for four more hours.…”

Section: Evaluation Of Immune Modulatory Effects Of Dendrobium Compoundsmentioning

confidence: 99%

“…Some of these metabolites exhibit a wide spectrum of pharmacological activities, including antioxidant, antiinflammatory, antidiabetic, antitumor, antimicrobial and neuroprotective activities [2,4]. For example, purified bibenzyls and phenanthrenes, such as chrysotoxine from D. pulchellum, cypripedin from D. densiflorum, gigantol from D. draconis and moscatilin from D. brymerianum, have been demonstrated to show promising inhibitory effects on human in vitro cell line models of lung cancer growth and metastasis [5][6][7][8][9]. However, whether these therapeutic effects can be also seen in primary human cells and/or in vivo remains to be investigated.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we aimed to investigate the immune modulatory activities on circulating monocytes of four known Dendrobium substances, which have already been shown to exert therapeutic effects in in vitro models of lung cancer [5][6][7][8][9], as well as one newly identified bibenzyl Dendrobium compound. All five compounds were isolated, purified and identified from Dendrobium lindleyi Steud, known in Thai as "Ueang Pueng" [23].…”

Section: Introductionmentioning

confidence: 99%

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Immune modulatory effect of a novel 4,5-dihydroxy-3,3´,4´-trimethoxybibenzyl from Dendrobium lindleyi

et al. 2020

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Dendrobium bibenzyls and phenanthrenes such as chrysotoxine, cypripedin, gigantol and moscatilin have been reported to show promising inhibitory effects on lung cancer growth and metastasis in ex vivo human cell line models, suggesting their potential for clinical application in patients with lung cancer. However, it remains to be determined whether these therapeutic effects can be also seen in primary human cells and/or in vivo. In this study, we comparatively investigated the immune modulatory effects of bibenzyls and phenanthrenes, including a novel Dendrobium bibenzyl derivative, in primary human monocytes. All compounds were isolated and purified from a Thai orchid Dendrobium lindleyi Steud, a new source of therapeutic compounds with promising potential of tissue culture production. We detected increased frequencies of TNF-and IL-6-expressing monocytes after treatment with gigantol and cypripedin, whereas chrysotoxine and moscatilin did not alter the expression of these cytokines in monocytes. Interestingly, the new 4,5-dihydroxy-3,3 0 ,4 0trimethoxybibenzyl derivative showed dose-dependent immune modulatory effects in lipopolysaccharide (LPS)-treated CD14 lo and CD14 hi monocytes. Together, our findings show immune modulatory effects of the new bibenzyl derivative from Dendrobium lindleyi on different monocyte sub-populations. However, therapeutic consequences of these different monocyte populations on human diseases including cancer remain to be investigated.

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Section: Evaluation Of Immune Modulatory Effects Of Dendrobium Compoundsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immune modulatory effect of a novel 4,5-dihydroxy-3,3´,4´-trimethoxybibenzyl from Dendrobium lindleyi

et al. 2020

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“…Bhummaphan et al investigated the suppressive effects of chrysotoxine on CSC-rich populations of H460 and H23 cells and primary CSCs in three-dimensional (3D) culture and showed that non-toxic doses (≤20 μM) of chrysotoxine inhibited CSC-like phenotypes and decreased CSC markers CD133, CD44, ABCG2 and ALDH1A1 which were mediated through a Src-AKT-Sox2-dependent mechanism (116).…”

Section: Natural Product Targeting Lung Cancer Stem Cellsmentioning

confidence: 99%

Lung Cancer Stem Cells and Cancer Stem Cell-targeting Natural Compounds

2018

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The novel information regarding molecular and translational research have created a paradigm shift in the understanding of lung cancer biology, revealing the more precise target for anti-cancer drug discovery. Lung cancer is a leading cause of cancer death worldwide accounting for approximately 1 in 5 of all cancer-related deaths. The most important causes of death in such a cancer involves the treatment failure as well as the spreading of cancer cells to distant sites which the cancer stem cell (CSC) within the tumor is accepted as a key driver. CSC is a rare special population of cancer cells exhibiting high tumorigenic properties together with self-renewal and differentiation capability. CSC is not only linked with high tumor-initiating activity, but is also implicated in chemotherapeutic resistance, metastasis, epithelial to mesenchymal transition, and recurrence. Thereafter, novel therapeutic strategies targeting these CSCs are considered in order to improve long-term clinical outcome. Here, we provide sufficient data regarding the biology of CSC in lung cancer, known CSC markers and cellular signals, and promising compounds targeting the stem cell signals in lung cancer that may benefit the development of novel anti-cancer treatment.

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“…The key benefits of natural compounds are the abundance of plants, compound diversity, and cost effectiveness. In focusing on CSCs and tumor growth inhibition, previous studies have reported the promising activities of the bibenzyl derivative chrysotoxine in the suppression of AKT and Src [18]. In vivo studies further revealed that the bibenzyl derivative moscatilin reduced tumor volumes of lung and esophageal cancer xenografts [19,20].…”

Section: Introductionmentioning

confidence: 99%

Gigantol Targets Cancer Stem Cells and Destabilizes Tumors via the Suppression of the PI3K/AKT and JAK/STAT Pathways in Ectopic Lung Cancer Xenografts

Losuwannarak

Maiuthed

Kitkumthorn

et al. 2019

Cancers

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Lung cancer has long been recognized as an important world heath concern due to its high incidence and death rate. The failure of treatment strategies, as well as the regrowth of the disease driven by cancer stem cells (CSCs) residing in the tumor, lead to the urgent need for a novel CSC-targeting therapy. Here, we utilized proteome alteration analysis and ectopic tumor xenografts to gain insight on how gigantol, a bibenzyl compound from orchid species, could attenuate CSCs and reduce tumor integrity. The proteomics revealed that gigantol affected several functional proteins influencing the properties of CSCs, especially cell proliferation and survival. Importantly, the PI3K/AKT/mTOR and JAK/STAT related pathways were found to be suppressed by gigantol, while the JNK signal was enhanced. The in vivo nude mice model confirmed that pretreatment of the cells with gigantol prior to a tumor becoming established could decrease the cell division and tumor maintenance. The results indicated that gigantol decreased the relative tumor weight with dramatically reduced tumor cell proliferation, as indicated by Ki-67 labeling. Although gigantol only slightly altered the epithelial-to-mesenchymal and angiogenesis statuses, the gigantol-treated group showed a dramatic loss of tumor integrity as compared with the well-grown tumor mass of the untreated control. This study reveals the effects of gigantol on tumor initiation, growth, and maintain in the scope that the cells at the first step of tumor initiation have lesser CSC property than the control untreated cells. This study reveals novel insights into the anti-tumor mechanisms of gigantol focused on CSC targeting and destabilizing tumor integrity via suppression of the PI3K/AKT/mTOR and JAK/STAT pathways. This data supports the potential of gigantol to be further developed as a drug for lung cancer.

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Cancer Stem Cell–Suppressing Activity of Chrysotoxine, a Bibenzyl fromDendrobium pulchellum

Cited by 27 publications

References 47 publications

Immune modulatory effect of a novel 4,5-dihydroxy-3,3´,4´-trimethoxybibenzyl from Dendrobium lindleyi

Immune modulatory effect of a novel 4,5-dihydroxy-3,3´,4´-trimethoxybibenzyl from Dendrobium lindleyi

Lung Cancer Stem Cells and Cancer Stem Cell-targeting Natural Compounds

Gigantol Targets Cancer Stem Cells and Destabilizes Tumors via the Suppression of the PI3K/AKT and JAK/STAT Pathways in Ectopic Lung Cancer Xenografts

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