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

Updated：2021-08-27

- Ethanol extract of Ilex hainanensis Merr. exhibits anti-melanoma activity by induction of G1/S cell-cycle arrest and apoptosis
- Chinese Journal of Integrative Medicine Vol. 24, Issue 1, Pages: 47-55(2018)
- 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
  CLC：
- Published：2018，
  
  Published Online：25 July 2017，
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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 24(1):47-55(2018)
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 24(1):47-55(2018) 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

references

Hoang MT, Eichenfield LF. The rising incidence of melanoma in children and adolescents. Dermatol Nurs 2000;12:183–192.

Siegel R, Miller K, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5–29.

Mouawad R, Sebert M, Michels J, Bloch J, Spano JP, Khayat D. Treatment for metastatic malignant melanoma: old drugs and new strategies. Crit Rev Oncol Hematol 2010;74:27–39.

Ives NJ, Stowe RL, Lorigan P, Wheatley K. Chemotherapy compared with biochemotherapy for the treatment of metastatic melanoma: a meta-analysis of 18 trials involving 2,621 patients. J Clin Oncol 2007;25:5426–5434.

Han SY, Li PP. Progress of research in antitumor mechanisms with Chinese medicine. Chin J Integr Med 2009;15:316–320.

Vickers A. Botanical medicines for the treatment of cancer: rationale, overview of current data, and methodological considerations for phase I and II trials. Cancer Invest 2002;20:1069–1079.

Johnson IT. Phytochemicals and cancer. Proc Nutr Soc 2007;66:207–215.

Qian YY, Zhang H, Hou Y, Yuan L, Li GQ, Guo SY, et al. Celastrus orbiculatus extract inhibits tumor angiogenesis by targeting vascular endothelial growth factor signaling pathway and shows potent antitumor activity in hepatocarcinomas in vitro and in vivo. Chin J Integr Med 2012;18:752–760.

Chen XQ, Zan K, Liu H, Yang J, Lai MX, Wang Q. Triterpenes and flavonoids from Ilex hainanensis Merr. (Aquifoliaceae). Biochem Syst Ecol 2009;37:678–682.

Yang J, Lv F, Chen XQ, Cui WX, Chen LH, Wen XD, et al. Pharmacokinetic study of major bioactive components in rats after oral administration of extract of Ilex hainanensis by highperformance liquid chromatography/electrospray ionization mass spectrometry. J Pharm Biomed Anal 2013;77:21–28.

Zhang CL, Cao QR. Tea-based traditional Chinese medicine resource—Shanlvcha. J Chin Med Mater (Chin) 1984;3:18–36.

Li JJ, Yang J, Cui WX, Chen XQ, Chen GL, Wen XD, et al. Analysis of therapeutic effect of Ilex hainanensis Merr. extract on nonalcoholic fatty liver disease through urine metabolite profiling by ultraperformance liquid chromatography/quadrupole time of flight mass spectrometry. Evid Based Complement Alternat Med 2013;2013:451975.

Yang H, Liu C, Zhang YQ, Ge LT, Chen J, Jia XQ, et al. Ilexgenin A induces B16-F10 melanoma cell G1/S arrest in vitro and reduces tumor growth in vivo. Int Immunopharmacol 2015;24:423–431.

Jin JL, Jing G, Yin TJ, Lu YJ, Xia JJ, Xie YY, et al. PTD4- apoptin protein and dacarbazine show a synergistic antitumor effect on B16-F1 melanoma in vitro and in vivo. Eur J Pharmacol 2011;654:17–25.

Rubin KM. Management of primary cutaneous and metastatic melanoma. Semin Oncol Nurs 2013;29:195–205.

Simões MCF, Sousa JJS, Pais AACC. Skin cancer and new treatment perspectives:a review. Cancer Lett 2015;357:8–42.

Flaherty KT. Targeting metastatic melanoma. Annu Rev Med 2012;63:171–183.

Mann J. Natural products in cancer chemotherapy: past, present and future. Nat Rev Cancer 2002;2:143–148.

Zhu YD, Liu YQ, Qian YY, Zhang H, Li GQ, Yang L. Extracts of Celastrus orbiculatus exhibit anti-proliferative and anti-invasive effects on human gastric adenocarcinoma cells. Chin J Integr Med 2014; 1–9.

Alley MC, Hollingshead MG, Dykes DJ, Waud WR. human tumor xenograft models in NCI drug development. In: Teicher BA, Andrews PA, eds. Anticancer drug development guide. Totowa, New Jersey: Humana Press;2004:125–152.

Zornig M, Hueber AO, Baum W, Evan G. Apoptosis regulators and their role in tumorigenesis. Biochim Biophys Acta 2001;1551:1–37.

Autret A, Martin SJ. Emerging role for members of the Bcl-2 family in mitochondrial morphogenesis. Mol Cell 2009;36:355–363.

Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 1999;18:6853–6866.

Nunez G, Benedict MA, Hu Y, Inohara N. Caspases: the proteases of the apoptotic pathway. Oncogene 1998;17:3237–3245.

Salvesen, Guy S. Caspases: opening the boxes and interpreting the arrows. Cell Death Differ 2002;9:3–5.

Ali Z, Fisher R, Larkin J. Targeted therapeutics in melanoma. Br J Cancer 2012;107:1663.

Paschke R, Heine M, S. Braun, Usadel KH. Mechanisms of hepatotoxicity caused by dacarbazine in rats. J Cancer Res Clin Oncol 1993;119:475–481.

Davar D, JM K. New therapies in the treatment of melanoma. Expert Opin Investig Drugs 2012;21:1643–1659.

Nikolaou VA, Stratigos AJ, Flaherty KT, Tsao H. Melanoma: new insights and new therapies. J Invest Dermatol 2012;132:854–863.

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Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine

Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine

Shanghai Key Laboratory of Complex Prescription

Chinese Medicine Hospital of Shanxi Province

Department of Gastroenterology, the Second Affiliated Hospital, Xi’an Jiaotong University

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