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Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Etlingera elatior Extract promotes cell death in B16 melanoma cells via down-regulation of ERK and Akt signaling pathways

Authors: Aungkana Krajarng, Malin Chulasiri, Ramida Watanapokasin

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

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Abstract

Background

Torch ginger (Etlingera elatior, EE) is a ginger plant that found in Southeast Asia. Previous study showed its flowers and leaves composed of several flavonoids with anti-cancer activity. This study aims to investigate the mechanism of EE extract on cell death induction in melanoma cells.

Methods

To carry out this study, the cytotoxic effect of EE extract was performed using MTT assay. Nuclear morphological change and loss of mitochondrial membrane potential were observed using Hoechst 33,342 and JC-1 staining. Flow cytometry using Annexin V/PI double staining assessed apoptosis, necrosis and viability. Caspase activity was detected by caspase activity kits. The expression of Bcl-2 family proteins, ERK and Akt signaling pathways were examined by Western blot analysis.

Results

The treatment of EE extract resulted in a dose- and time-dependent reduction in cell viability in B16 cells. It also induced nuclear condensation, phosphatidylserine exposure, and loss of mitochondrial membrane potential, which are markers of apoptosis. Furthermore, the expression of Bim was increased instead of Bax and Bcl-2. The results also showed caspase-independent activity and the down-regulation of ERK and Akt signaling pathway.

Conclusion

The results suggest that EE extract induced caspase-independent cell death via down-regulation of ERK and Akt pathways in B16 cells. This may be beneficial as a chemopreventive or chemotherapeutic agent in melanoma treatment.
Literature
1.
go back to reference Scherer D, Kumar R. Genetics of pigmentation in skin cancer-a review. Mutat Res. 2010;705:141–53.CrossRefPubMed Scherer D, Kumar R. Genetics of pigmentation in skin cancer-a review. Mutat Res. 2010;705:141–53.CrossRefPubMed
2.
go back to reference Bhatia S, Tykodi S, Thompson A. Treatment of metastatic melanoma: an overview. Oncology (Williston Park). 2009;23(6):488–96. Bhatia S, Tykodi S, Thompson A. Treatment of metastatic melanoma: an overview. Oncology (Williston Park). 2009;23(6):488–96.
3.
go back to reference Yin SY, Wei WC, Jian FY, Yang NS. Therapeutic applications of herbal medicines for cancer patients. Evid Based Complement Alternat Med 2013;2013:302426. doi:https://doi.org/10.1155/2013/302426. Yin SY, Wei WC, Jian FY, Yang NS. Therapeutic applications of herbal medicines for cancer patients. Evid Based Complement Alternat Med 2013;2013:302426. doi:https://​doi.​org/​10.​1155/​2013/​302426.
4.
go back to reference Ibrahim H. Kaempferia. In: de Padua LS, Bunyapraphatsara N, Lemmens RHMJ, editors. Plant resources of South-East Asia, Netherlands: Backhuys Publisher, vol. 12; 1999. p. 331–5. Ibrahim H. Kaempferia. In: de Padua LS, Bunyapraphatsara N, Lemmens RHMJ, editors. Plant resources of South-East Asia, Netherlands: Backhuys Publisher, vol. 12; 1999. p. 331–5.
5.
go back to reference Ibrahim H, Setyowati FM. Etlingera. In: de Guzman CC, Siemonsma JS, editors. Plant resources of South-East Asia, Pudoc, Wageningen, vol. 13; 1999. p. 123–6. Ibrahim H, Setyowati FM. Etlingera. In: de Guzman CC, Siemonsma JS, editors. Plant resources of South-East Asia, Pudoc, Wageningen, vol. 13; 1999. p. 123–6.
6.
go back to reference Chan EWC, Lim YY, Wong SK. Phytochemistry and pharmacological properties of Etlingera elatior: a review. Phcog J. 2011;3(22):1–6.CrossRef Chan EWC, Lim YY, Wong SK. Phytochemistry and pharmacological properties of Etlingera elatior: a review. Phcog J. 2011;3(22):1–6.CrossRef
7.
go back to reference Maimulyanti A, Prihadi AR. Chemical composition, phytochemical and antioxidant activity from extract of Etlingera elatior flower from Indonesia. J Pharmacogn Phytochem. 2015;3(6):233–8. Maimulyanti A, Prihadi AR. Chemical composition, phytochemical and antioxidant activity from extract of Etlingera elatior flower from Indonesia. J Pharmacogn Phytochem. 2015;3(6):233–8.
8.
go back to reference Chan EWC, Lim YY, Wong LF, Lianto FS, Wong SK, Lim KK, et al. Antioxidant and tyrosinase inhibition properties of leaves and rhizomes of ginger species. Food Chem. 2008;109:477–83.CrossRef Chan EWC, Lim YY, Wong LF, Lianto FS, Wong SK, Lim KK, et al. Antioxidant and tyrosinase inhibition properties of leaves and rhizomes of ginger species. Food Chem. 2008;109:477–83.CrossRef
9.
go back to reference Chan EWC, Lim YY, Omar M. Antioxidant and antibacterial activity of leaves of Etlingera species (Zingiberaceae) in peninsular Malaysia. Food Chem. 2007;104:1586–93.CrossRef Chan EWC, Lim YY, Omar M. Antioxidant and antibacterial activity of leaves of Etlingera species (Zingiberaceae) in peninsular Malaysia. Food Chem. 2007;104:1586–93.CrossRef
10.
go back to reference Punnawich Y, Montree I, Warin I, Kan C. Antifungal effects of Thai medicinal plants against Collectotrichum gloeosporioides Penz. Philip Agric Sci. 2009;92:265–70. Punnawich Y, Montree I, Warin I, Kan C. Antifungal effects of Thai medicinal plants against Collectotrichum gloeosporioides Penz. Philip Agric Sci. 2009;92:265–70.
11.
go back to reference Mackeen MM, Ali AM, El-Sharkawy SH, Manap MY, Salleh KM, Lajis NH, et al. Antimicrobial and cytotoxic properties of some Malaysian traditional vegetables (ulam). Pharm Biol. 1997;35:174–8.CrossRef Mackeen MM, Ali AM, El-Sharkawy SH, Manap MY, Salleh KM, Lajis NH, et al. Antimicrobial and cytotoxic properties of some Malaysian traditional vegetables (ulam). Pharm Biol. 1997;35:174–8.CrossRef
12.
go back to reference Habsah M, Ali AM, Lajis NH, Sukari MA, Yap YH, Kikuzaki H, et al. Antitumour promoting and cytotoxic constituents of Etlingera elatior. Malay J Med Sci. 2005;12:6–12. Habsah M, Ali AM, Lajis NH, Sukari MA, Yap YH, Kikuzaki H, et al. Antitumour promoting and cytotoxic constituents of Etlingera elatior. Malay J Med Sci. 2005;12:6–12.
13.
go back to reference Chan EWC, Lim YY, Ling SK, Tan SP, Lim KK, Khoo MGH. Caffeoylquinic acids from leaves of Etlingera species (Zingiberaceae). LWT-Food Sci Technol. 2009;42:1026–30.CrossRef Chan EWC, Lim YY, Ling SK, Tan SP, Lim KK, Khoo MGH. Caffeoylquinic acids from leaves of Etlingera species (Zingiberaceae). LWT-Food Sci Technol. 2009;42:1026–30.CrossRef
14.
go back to reference Thuncharoen W, Chulasiri M, Nilwarangkoon S, Nakamura Y, Watanapokasin R. Apoptotic induction of skin cancer cell death by plant extracts. J Med Assoc Thail. 2013;96(Suppl 1):S60–4. Thuncharoen W, Chulasiri M, Nilwarangkoon S, Nakamura Y, Watanapokasin R. Apoptotic induction of skin cancer cell death by plant extracts. J Med Assoc Thail. 2013;96(Suppl 1):S60–4.
15.
go back to reference Kuo SM. Dietary flavonoids and cancer prevention: evidence and potential mechamisma. Crit Rev Oncog. 1997;8:47–69.CrossRefPubMed Kuo SM. Dietary flavonoids and cancer prevention: evidence and potential mechamisma. Crit Rev Oncog. 1997;8:47–69.CrossRefPubMed
16.
17.
go back to reference Iwashita K, Kobori M, Yamaki K, Tsushida T. Flavonoids inhibit cell growth and induce apoptosis in B16 melanma 4A5 cells. Biosci Biotechnol Biochem. 2000;64:1813–20.CrossRefPubMed Iwashita K, Kobori M, Yamaki K, Tsushida T. Flavonoids inhibit cell growth and induce apoptosis in B16 melanma 4A5 cells. Biosci Biotechnol Biochem. 2000;64:1813–20.CrossRefPubMed
18.
go back to reference Zhang X, Chen J, Xia Y, Xu Q. Apoptosis of murine melanoma B16-BL6 cells induced by quercetin targeting mitochondria, inhibiting expression of PKC-α and translocating PKC-δ. Cancer Chemother Pharmacol 2005;55:251 262. Zhang X, Chen J, Xia Y, Xu Q. Apoptosis of murine melanoma B16-BL6 cells induced by quercetin targeting mitochondria, inhibiting expression of PKC-α and translocating PKC-δ. Cancer Chemother Pharmacol 2005;55:251 262.
20.
go back to reference Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2:647–56.CrossRefPubMed Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2:647–56.CrossRefPubMed
21.
go back to reference Wang YF, Jiang CC, Kiejda KA, Gillespie S, Zhang XD, Hersey P. Apoptosis induction in human melanoma cells by inhibition of MEK is caspase-independent and mediated by the Bcl-2 family members PUMA, Bim, and mcl-1. Clin Cancer Res. 2007;13(16):4934–42.CrossRefPubMed Wang YF, Jiang CC, Kiejda KA, Gillespie S, Zhang XD, Hersey P. Apoptosis induction in human melanoma cells by inhibition of MEK is caspase-independent and mediated by the Bcl-2 family members PUMA, Bim, and mcl-1. Clin Cancer Res. 2007;13(16):4934–42.CrossRefPubMed
22.
go back to reference Cregan SP, Dawson VL, Slack RS. Role of AIF in caspase-dependent and caspase-independent cell death. Oncogene. 2004;23:2785–96.CrossRefPubMed Cregan SP, Dawson VL, Slack RS. Role of AIF in caspase-dependent and caspase-independent cell death. Oncogene. 2004;23:2785–96.CrossRefPubMed
23.
go back to reference Li LY, Luo X, Wang X. Endonuclease G is an apoptotic DNase when release from mitochondria. Nature. 2001;412(6842):95–9.CrossRefPubMed Li LY, Luo X, Wang X. Endonuclease G is an apoptotic DNase when release from mitochondria. Nature. 2001;412(6842):95–9.CrossRefPubMed
24.
go back to reference Balmanno K, Cook SJ. Tumour cell survival signalling by the ERK1⁄2 pathway. Cell Death Differ. 2009;16:368–77.CrossRefPubMed Balmanno K, Cook SJ. Tumour cell survival signalling by the ERK1⁄2 pathway. Cell Death Differ. 2009;16:368–77.CrossRefPubMed
25.
go back to reference Gillings AS, Balmanno K, Wiggins C, Johnson M, Cook SJ. Apoptosis and autophagy: BIM as a mediator of tumour cell death in response to oncogene-targeted therapeutics. FEBS J. 2009;276:6050–62.CrossRefPubMed Gillings AS, Balmanno K, Wiggins C, Johnson M, Cook SJ. Apoptosis and autophagy: BIM as a mediator of tumour cell death in response to oncogene-targeted therapeutics. FEBS J. 2009;276:6050–62.CrossRefPubMed
26.
go back to reference Zhang XD, Borrow JM, Zhang XY, Nguyen T, Hersey P. Activation of ERK1/2 protects melanoma cells from TRAIL-induced apoptosis by inhibiting Smac/DIABLO release from mitochondria. Oncogene. 2003;22:2869–81.CrossRefPubMed Zhang XD, Borrow JM, Zhang XY, Nguyen T, Hersey P. Activation of ERK1/2 protects melanoma cells from TRAIL-induced apoptosis by inhibiting Smac/DIABLO release from mitochondria. Oncogene. 2003;22:2869–81.CrossRefPubMed
27.
go back to reference Zhuang L, Lee CS, Scolyer RA, McCarthy SW, Palmer AA, Zhang XD, et al. Activation of the extracellular signal regulated kinase (ERK) pathway in human melanoma. J Clin Pathol. 2005;58:1163–9.CrossRefPubMedPubMedCentral Zhuang L, Lee CS, Scolyer RA, McCarthy SW, Palmer AA, Zhang XD, et al. Activation of the extracellular signal regulated kinase (ERK) pathway in human melanoma. J Clin Pathol. 2005;58:1163–9.CrossRefPubMedPubMedCentral
28.
go back to reference Merat R, Seyde O, Fernandez E, Kaya G. Multiple palpebral syringomas occurring after initiation of BRAF inhibition therapy in a patient with metastatic melanoma. JAAD Case Reports. 2016;2:482–4.CrossRefPubMedPubMedCentral Merat R, Seyde O, Fernandez E, Kaya G. Multiple palpebral syringomas occurring after initiation of BRAF inhibition therapy in a patient with metastatic melanoma. JAAD Case Reports. 2016;2:482–4.CrossRefPubMedPubMedCentral
29.
go back to reference Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012;366:207–15.CrossRefPubMedPubMedCentral Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012;366:207–15.CrossRefPubMedPubMedCentral
30.
go back to reference McArthur GA. Combination therapies to inhibit the RAF/MEK/ERK pathway in melanoma: we are not done yet. Front Oncol. 2015;15:161. McArthur GA. Combination therapies to inhibit the RAF/MEK/ERK pathway in melanoma: we are not done yet. Front Oncol. 2015;15:161.
31.
go back to reference Jiang CC, Lai F, Tay KH, Croft A, Rizos H, Becker TM, et al. Apoptosis of human melanoma cells induced inhibition of B-RAFV600E involves preferential splicing of bims. Cell Death Dis. 2010;1(9):e69.CrossRefPubMedPubMedCentral Jiang CC, Lai F, Tay KH, Croft A, Rizos H, Becker TM, et al. Apoptosis of human melanoma cells induced inhibition of B-RAFV600E involves preferential splicing of bims. Cell Death Dis. 2010;1(9):e69.CrossRefPubMedPubMedCentral
32.
go back to reference Lou M, Zhang LN, Ji PG, Feng FQ, Liu JH, Yang C, et al. Quercetin nanoparticles induced autophagy and apoptosis through AKT/ERK/caspase-3 signaling pathway in human neuroglioma cells: in vitro and in vivo. Biomed Pharmacother. 2016;84:1–9.CrossRefPubMed Lou M, Zhang LN, Ji PG, Feng FQ, Liu JH, Yang C, et al. Quercetin nanoparticles induced autophagy and apoptosis through AKT/ERK/caspase-3 signaling pathway in human neuroglioma cells: in vitro and in vivo. Biomed Pharmacother. 2016;84:1–9.CrossRefPubMed
33.
go back to reference Lou X, Sun B, Song J, Wang Y, Jaing J, Xu Y, et al. Human sulfatase 1 exerts anti-tumor activity by inhibiting the AKT/ CDK4 signaling pathway in melanoma. Oncotarget. 2016;7(51):84486–95.PubMedPubMedCentral Lou X, Sun B, Song J, Wang Y, Jaing J, Xu Y, et al. Human sulfatase 1 exerts anti-tumor activity by inhibiting the AKT/ CDK4 signaling pathway in melanoma. Oncotarget. 2016;7(51):84486–95.PubMedPubMedCentral
34.
go back to reference Rafiq RA, Quadri A, Nazir LA, Peerzada K, Ganai BA, Tasduq SA. A potent inhibitor of phosphoinositide 3-kinase (PI3K) and mitogen activated protein (MAP) kinase Signalling, quercetin (3, 3′, 4′, 5, 7-Pentahydroxyflavone) promotes cell death in ultraviolet (UV)-B-irradiated B16F10 melanoma cells. PLoS One. 2015;10(7):e0131253.CrossRefPubMedPubMedCentral Rafiq RA, Quadri A, Nazir LA, Peerzada K, Ganai BA, Tasduq SA. A potent inhibitor of phosphoinositide 3-kinase (PI3K) and mitogen activated protein (MAP) kinase Signalling, quercetin (3, 3′, 4′, 5, 7-Pentahydroxyflavone) promotes cell death in ultraviolet (UV)-B-irradiated B16F10 melanoma cells. PLoS One. 2015;10(7):e0131253.CrossRefPubMedPubMedCentral
Metadata
Title
Etlingera elatior Extract promotes cell death in B16 melanoma cells via down-regulation of ERK and Akt signaling pathways
Authors
Aungkana Krajarng
Malin Chulasiri
Ramida Watanapokasin
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-1921-y

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