Ethanol extract of Ilex hainanensis Merr. exhibits anti-melanoma activity by induction of G1/S cell-cycle arrest and apoptosis

Zhang, Yaqi; Yang, Hao; Sun, Weiyi; Wang, Juan; Zhang, Bao-yuan; Shen, Yanjun; Yin, Min-qiang; Liu, Yunxing; Liu, Chang; Sun, Yuanming

doi:10.1007/s11655-017-2544-8

Cited by 8 publications

(4 citation statements)

References 28 publications

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“…In addition, curcumin, bark hormone, oridonin, matrine, and oleanolic acid have shown strong antitumor activity in preclinical studies 14. Moreover, studies have demonstrated that IME exhibited significant antimelanoma activity in vitro and in vivo 15…”

Section: Discussionmentioning

confidence: 99%

Ilex hainanensis Merr targets ITGAV to suppress the proliferation and metastasis of osteosarcoma cells

Pei¹,

Zhang²,

Zheng³

et al. 2019

OTT

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Background: Osteosarcoma (OS) is the most common primary malignant bone tumor. Hence, there is an urgent need to identify effective and safe therapeutic agents against OS. It has been reported that Ilex hainanensis Merr (IME) possesses antitumor properties. Integrin subunit alpha V (ITGAV) is important for the diagnosis, treatment, and prognosis of tumors. Purpose: The objective of this study was to whether IME can play a role in the treatment of osteosarcoma by regulating ITGAV. Methods: Western blot and real-time PCR were used to detect the expression of ITGAV in non-tumorous tissues, osteosarcoma tissues, and metastatic tumors. The expression of ITGAV in MG63, U2OS, and hFOB1. A total of 19 cells was determined through Western blotting and real-time PCR. The expression of ITGAV in OS cells treated with different concentrations of DDP was determined through Western blotting. Agter transfecting with control or si-ITGAV, and subsequently treated with control or 5 μmol/L DDP, MTT assay and transwell assay were used to detect the proliferaion and migration of cells. Western blot was used to detect the expression of ITGAV in cells treated with different concentrations of IME and MTT assay and transwell assay were used to detect the proliferaion and migration of cells. MG63 and U2OS cells were treated with control, 5 μmol/L DDP, 25 μmol/L IME, or 5 μmol/L DDP combined with 25 μmol/L IME, the expression of ITGAV was determined through Western blotting and real-time PCR. MTT assay and transwell assay were used to detect the proliferation and migration of cells. Inhibitory effect of IME on lung metastasis of osteosarcoma in vivo. Results: ITGAV was highly expressed in tumors, with the highest expression found in metastatic tumors and higher in OS cells. A low concentration of DDP (5 μmol/L) inhibited the expression of ITGAV. However, ITGAV may be related to the development of resistance to DDP. Silencing of ITGAV downregulates the proliferation and migration of OS cells as the effect of low-concentration DDP (5 μmol/L). IME inhibited the proliferation and migration of MG63 and U2OS cells in a concentration-dependent manner and decreased the expression of ITGAV. MTT and Transwell assays showed that 25 μmol/L IME and 5 μmol/L DDP exhibited similar inhibitory effects on the proliferation and migration of OS cells. The combination of IME with DDP resulted in the amplification of these inhibitory effects. Both DDP and IME downregulated the expression of ITGAV, and the inhibition of ITGAV was amplified by the combination of IME with DDP. In-vivo studies have shown that IME and DDP, independently or in combination, may significantly inhibit the metastasis of OS to the lungs. Conclusion: IME may reduce the resistance of OS cells to DDP to some extent.

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Section: Discussionmentioning

confidence: 99%

Ilex hainanensis Merr targets ITGAV to suppress the proliferation and metastasis of osteosarcoma cells

Pei¹,

Zhang²,

Zheng³

et al. 2019

OTT

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“…Therefore, there is no deleterious side effect on melanoma when nanomolar TTX is applied as a pain-killer. On the other hand, TTX is used to identify Na + channel subtypes ( 22 , 23 ). While Na v 1.5 had a median effective concentration of TTX at 5.7 µM, the median effective concentrations of TTX to Na v 1.8 and Na v 1.9 are 60 and 40 µM respectively ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

Functional cardiac Na+ channels are expressed in human melanoma cells

et al. 2018

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Resting membrane potential (RMP) and intracellular Ca2+ concentration [(Ca2+)i] are involved in tumorigenesis and metastasis. The present study investigated whether functional cardiac Na+ channels are expressed in human melanoma cells (WM 266-4) and its nonmalignant human melanocytes (HMC), as well as whether they participate in RMP maintenance and Ca2+ homeostasis. Confocal microscopy and western blot analysis were used to detect Na+ channels. The patch-clamp technique was employed to record Na+ currents and action potentials. Cytoplasmic Ca2+ was measured by loading Fluo-4. Cardiac (Nav1.5) Na+ channels were expressed in HMCs and WM 266-4 cells. Tetrodotoxin (TTX) dose-dependently blocked Na+ currents in WM 266-4 while HMCs had no Na+ currents. Ultraviolet light induced similar action potentials in HMCs and WM 266-4 cells, which were abolished by transient receptor potential A1 channel-specific blocker, HC-030031. Compared with HMCs, RMP was substantially depolarized in WM 266-4. TTX hyperpolarized RMP in WM 266-4 cells at a concentration of 30 µM, which facilitated Ca2+ influx. Compared with HMCs, (Ca2+)i was significantly higher in WM 266-4 cells and was elevated by 30 µM TTX. Collectively, Cardiac Na+ channels depolarize RMP and inhibit Ca2+ uptake in melanoma cells possibly contributing to tumorigenesis and metastasis. Na+ channel agonists may be developed to treat melanoma such as WM 266-4.

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“…Other species, such as I. asprella [9] and I. hainanensis Merr. [35], are used as folk medicines. More than 20 Chinese Ilex species have medicinal uses recorded [36].…”

Section: Hollies Utilized As Sources Of Medicinesmentioning

confidence: 99%

Utilization of the Hollies (Ilex L. spp.): A Review

Yao

Zhang

Corlett

2022

Forests

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The hollies (Ilex L., Aquifoliaceae) form a large (>669 spp.) genus of forest trees and shrubs, which is almost cosmopolitan in mesic environments but most diverse in subtropical China and montane South America. Throughout the range of the genus, Ilex species have been utilized as beverages, medicines, ornamentals, honey plants, timber, and for various other minor uses. Recent studies on the genomics, evolution, and biogeography of Ilex now make it possible to take a systematic approach to understanding and expanding the economic importance of the genus, but information on existing uses is scattered among numerous published and unpublished sources. We therefore review the existing literature on utilization of Ilex species, supplementing this with information from the grey literature and product websites. We show that, despite the number and diversity of known uses, most Ilex species are not known to be utilized at present, suggesting considerable unrealized potential. We highlight gaps in our knowledge and opportunities for expanded usage. Finally, we discuss how the availability of a new phylogeny and whole genome can assist screening of additional wild species for economic potential and facilitate breeding programs for species already under cultivation.

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Ethanol extract of Ilex hainanensis Merr. exhibits anti-melanoma activity by induction of G1/S cell-cycle arrest and apoptosis

Abstract: IME exhibited significant anti-melanoma activity in vitro and in vivo, suggesting that IME might be a promising effective candidate with lower toxic for malignant melanoma therapy.

Cited by 8 publications

References 28 publications

<p><em>Ilex hainanensis Merr</em> targets ITGAV to suppress the proliferation and metastasis of osteosarcoma cells</p>

<p><em>Ilex hainanensis Merr</em> targets ITGAV to suppress the proliferation and metastasis of osteosarcoma cells</p>

Functional cardiac Na+ channels are expressed in human melanoma cells

Utilization of the Hollies (Ilex L. spp.): A Review

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