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

Ya-qi Zhang; Hao Yang; Wei-dong Sun; Juan Wang; Bao-yuan Zhang; Yan-jun Shen; Min-qiang Yin; Yun-xing Liu; Chang Liu; Yun Sun

doi:10.1007/s11655-017-2544-8

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

OriginalPaper | Updated：2021-08-27

- Ethanol extract of Ilex hainanensis Merr. exhibits anti-melanoma activity by induction of G1/S cell-cycle arrest and apoptosis
- Ethanol extract of Ilex hainanensis Merr. exhibits anti-melanoma activity by induction of G1/S cell-cycle arrest and apoptosis
- 中国结合医学杂志（英文版） 2018年24卷第1期页码：47-55
- Affiliations：
  
  1. College of Medicine, Yangzhou University,Jiangsu Province,Yangzhou,China
  2. College of Clinical Chinese Medicine, Yangzhou University,Jiangsu Province,Yangzhou,China
  3. Medical and Pharmaceutical Institute, Yangzhou University,Jiangsu Province,Yangzhou,China
  4. Chinese Medicine Hospital of Yangzhou City,Jiangsu Province,Yangzhou,China
  5. Oncology Business Unit, Wuxi AppTec. Inc,Shanghai,China
- Author bio：
- Funds：
- DOI：10.1007/s11655-017-2544-8
  中图分类号：
- 纸质出版日期：2018，
  
  网络出版日期：2017-7-25，
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Zhang, Yq., Yang, H., Sun, Wd. et al. Ethanol extract of Ilex hainanensis Merr. exhibits anti-melanoma activity by induction of G1/S cell-cycle arrest and apoptosis., Chin. J. Integr. Med. 24, 47–55 (2018). https://doi.org/10.1007/s11655-017-2544-8

Ya-qi Zhang, Hao Yang, Wei-dong Sun, et al. Ethanol extract of Ilex hainanensis Merr. exhibits anti-melanoma activity by induction of G1/S cell-cycle arrest and apoptosis[J]. Chinese Journal of Integrative Medicine, 2018,24(1):47-55.
Zhang, Yq., Yang, H., Sun, Wd. et al. Ethanol extract of Ilex hainanensis Merr. exhibits anti-melanoma activity by induction of G1/S cell-cycle arrest and apoptosis., Chin. J. Integr. Med. 24, 47–55 (2018). https://doi.org/10.1007/s11655-017-2544-8 DOI：

Ya-qi Zhang, Hao Yang, Wei-dong Sun, et al. Ethanol extract of Ilex hainanensis Merr. exhibits anti-melanoma activity by induction of G1/S cell-cycle arrest and apoptosis[J]. Chinese Journal of Integrative Medicine, 2018,24(1):47-55. DOI： 10.1007/s11655-017-2544-8.

摘要

To evaluate anti-melanoma effect of ethanol extract of Ilex hainanensis Merr. (IME) and elucidate its underlying mechanism. Thirty-six tumor-bearing mice were randomized into 6 groups (n=6) as follows: model group

IME 25

100

and 200 mg/kg groups and dacarbazine (DTIC) 70 mg/kg group. The mice in the IME treatment groups were intragastrically administered with IME 25

100 or 200 mg/kg per day

respectively. The mice in the DTIC group were intraperitoneally injected with DTIC 70 mg/kg every 2 days. The drug administration was lasting for 14 days. The cell viability was evaluated by 3-(4

5-dime-thylthylthiazol-2-yl)-2

5-diphenyl-tetrazolium bromide (MTT) assay. Flow cytometry was employed to detect cell cycle and apoptosis. The gene and protein expressions of nuclear factor κB-p65 (NF-κB-p65)

Bcl-2

B-cell lymphomaextra large (Bcl-xL) and Bax were detected by quantitative real-time polymerase chain reaction and Western blot analyses. Caspases-3

-8

and -9 activities were detected using the colorimetric method. In addition

a B16-F10 melanoma xenograft mouse model was used to evaluate the anti-cancer activity of IME in vivo. Furthermore

a survival experiment of tumor-bearing mice was also performed to evaluate the possible toxicity of IME. IME significantly inhibited the proliferation of B16-F10 cells (P<0.01). Flow cytometric analysis showed that IME induced G1/S cell cycle arrest and apoptosis (both P<0.01). IME inhibited activation of NF-κB

decreased the gene and protein expressions of Bcl-2

Bcl-xL

and increased the gene and protein expressions of Bax (all P<0.01). In addition

IME induced the activation of Caspases-3

-8

and -9 in B16-F10 cells. The study in vivo showed that IME significantly reduced tumor volume (P<0.01)

and the inhibitory rate came up to 68.62%. IME also induced large areas of necrosis and intra-tumoral apoptosis that correlated with a reduction in tumor volume. Survival experiment showed that treatment with IME for 14 days significantly prolonged survival time and 20% of mice in the IME 200 mg/kg group were still alive until the 50th day. Notably

IME showed no apparent side-effects during the treatment period. 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.

Abstract

IME 25

100

and 200 mg/kg groups and dacarbazine (DTIC) 70 mg/kg group. The mice in the IME treatment groups were intragastrically administered with IME 25

100 or 200 mg/kg per day

respectively. The mice in the DTIC group were intraperitoneally injected with DTIC 70 mg/kg every 2 days. The drug administration was lasting for 14 days. The cell viability was evaluated by 3-(4

5-dime-thylthylthiazol-2-yl)-2

5-diphenyl-tetrazolium bromide (MTT) assay. Flow cytometry was employed to detect cell cycle and apoptosis. The gene and protein expressions of nuclear factor κB-p65 (NF-κB-p65)

Bcl-2

B-cell lymphomaextra large (Bcl-xL) and Bax were detected by quantitative real-time polymerase chain reaction and Western blot analyses. Caspases-3

-8

and -9 activities were detected using the colorimetric method. In addition

a B16-F10 melanoma xenograft mouse model was used to evaluate the anti-cancer activity of IME in vivo. Furthermore

decreased the gene and protein expressions of Bcl-2

Bcl-xL

and increased the gene and protein expressions of Bax (all P<0.01). In addition

IME induced the activation of Caspases-3

-8

and -9 in B16-F10 cells. The study in vivo showed that IME significantly reduced tumor volume (P<0.01)

IME showed no apparent side-effects during the treatment period. 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.

关键词

Ilex hainanensis Merr.anti-melanoma activityG1/S arrestapoptosisSurvival TimecaspaseChinese Medicine

Keywords

Ilex hainanensis Merr.anti-melanoma activityG1/S arrestapoptosisSurvival TimecaspaseChinese Medicine

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