Brucea javanica Leaf Extract Induced Apoptosis in Human Oral Squamous Cell Carcinoma (HSC2) Cells by Attenuation of Mitochondrial Membrane Permeability

Britanto Dani Wicaksono, Enos Tangkearung, Ferry Sandra

Abstract


BACKGROUND: Brucea javanica extract has been reported to have anti-proliferative and cell death induction activities. B. javanica extract was reported to induce apoptosis through caspase cascade. Most of investigated B. javanica extracts were derived from seeds and fruits, or commercially available oil emulsion. Therefore we conducted a study on B. javanica leaf extract (BJLE) in oral cancer cells.

METHODS: B. javanica leaves were collected, identified, minced, dried, extracted with distilled ethanol at room temperature for 24 hours, filtered and evaporated. Resulted BJLE was stored at 4°C. Human oral squamous cell carcinoma (HSC)-2 cells were fasted for 12 hours and treated with BJLE in various concentrations for 24 hours. Cells were then quantified with 3-(4,5-dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium bromide (MTT) assay, demonstrated with 4',6'-diamidino-2-phenylindole (DAPI) staining. To find out mitochondrial membrane permeability (MMP), mitochondrial membrane potential (ΔΨM) was analyzed.

RESULTS: BJLE reduced percentage of viable HSC-2 cells in a concentration dependent manner. BJLE induced apoptosis in HSC-2 cells. With treatment of 50 μg/ml BJLE, fragmented nuclei were seen. ΔΨM of HSC-2 cells treated with 50 μg/ml BJLE were shifted to the left, meaning that BJLE induced reduction of ΔΨM and attenuation of MMP.

CONCLUSION: Our results suggested that BJLE could induce apoptosis by attenuating MMP.

KEYWORDS: Brucea javanica, leaf, apoptosis, HSC-2, MTT, DAPI, mitochondria, permeability


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References


Zhao L, Li C, Zhang Y, Wen Q, Ren D. Phytochemical and biological activities of an anticancer plant medicine: Brucea javanica. Anticancer Agents Med Chem. 2014; 14: 440-58, CrossRef.

Bawm S, Matsuura H, Elkhateeb A, Nabeta K, Subeki, Nonaka N, et al. in vitro antitrypanosomal activities of quassinoid compounds from the fruits of a medicinal plant, Brucea javanica. Vet Parasitol. 2008; 158: 288-94, CrossRef.

Wu T, Abudou M, Chen S. Evidence-based anticancer materia medica for esophageal cancer. In: Cho WCS, editor. Materia Medica for Various Cancers. New York: Springer; 2012. p.151-70, CrossRef.

Zhang H, Yang JY, Zhou F, Wang LH, Zhang W, Sha S, et al. Seed oil of Brucea javanica induces apoptotic death of acute myeloid leukemi cells via both the death receptors and the mitochondrialrelated pathways. Evid Based Complement Alternat Med. 2011; 2011: 1-14, CrossRef.

Wang F, Qin W, Zhang G, Zhang Y, Liu H, Yang L, et al. Prospective clinical studies at the eficacy of Brucea javanica oil, mitomycin and BCG for preventing postoperative relapse of supericial bladder cancer through perfusion. China-German J Clin Oncol. 2011; 10: 228-31, CrossRef.

Cui Y, Wu Z, Liu X, Ni R, Zhu X, Ma L, et al. Preparation, safety, pharmacokinetics, and pharmacodynamics of liposomes containing Brucea javanica oil. AAPS PharmSciTech. 2010; 11: 878-84, CrossRef.

Yu YL, Lu Y, Tang X, Cui FD. Formulation, preparation and evaluation of an intravenous emulsion containing Brucea javanica oil and Coix Seed oil for anti-tumor application. Biol Pharm Bull. 2008; 31: 673-80, CrossRef.

Su Z, Hao J, Xu Z, Huang R, Zhang N, Qiu S. A new quassinoid from fruits of Brucea javanica. Nat Prod Res. 2013; 27: 2016-21, CrossRef.

Gao H, Lamusta J, Zhang WF, Salmonsen R, Liu Y, O’Connell E, t al. Tumor cell selective cytotoxicity and apoptosis induction by an herbal preparation from Brucea javanica. N Am J Med Sci. 2011; 4: 62-6, CrossRef.

Pan L, Chin YW, Chai HB, Ninh TN, Soejarto DD, Kinghorn AD. Bioactivity-guided isolation of cytotoxic constituents of Brucea javanica collected in Vietnam. Bioorg Med Chem. 2009; 74: 2219- 24, CrossRef.

Lau FY, Chui CH, Gambari R, Kok SH, Kan KL, Cheng GY, et al. Antiproliferative and apoptosis-inducing activity of Brucea javanica extract on human carcinoma cells. Int J Mol Med. 2005; 16: 1157-62, CrossRef.

Lau ST, Lin ZX, Zhao M, Leung PS. Brucea javanica fruit induces cytotoxicity and apoptosis in pancreatic adenocarcinoma cell lines. Phytother Res. 2008; 22: 477-86, CrossRef.

Lau ST, Lin ZX, Liao Y, Zhao M, Cheng CH, Leung PS. Bruceine D induces apoptosis in pancreatic adenocarcinoma cell line PANC-1 through the activation of p38-mitogen activated protein kinase. Cancer Lett. 2009; 281: 42-52, CrossRef.

Liu L, Lin ZX, Leung PS, Chen LH, Zhao M, Liang J. Involvement of the mitochondrial pathway in bruceine D-induced apoptosis in Capan-2 human pancreatic adenocarcinoma cells. Int J Mol Med. 2012; 30: 93-9, CrossRef.

Lou GG, Yao HP, Xie LP. Brucea javanica oil induces apoptosis in T24 bladder cancer cells via upregulation of caspase-3, caspase-9, and inhibition of NF-kappaB and COX-2 expressions. Am J Chin Med. 2010; 38: 613-24. CrossRef.

Yan Z, Zhang B, Huang Y, Qiu H, Chen P, Guo GF. Involvement of autophagy inhibition in Brucea javanica oil emulsion-induced colon cancer cell death. Oncol Lett. 2015; 9: 1425-31, CrossRef.

Majid MZ, Zaini ZM, Razak FA. Apoptosis-inducing effect of three medicinal plants on oral cancer cells KB and ORL-48. Scientific World Journal. 2014; 2014: 125353, CrossRef.

Widowati W, Tjandrawati M, Risdian C, Ratnawati H, Tjahjani S, Sandra F. The comparison of antioxidative and proliferation inhibitor properties of Piper betle L., Catharanthus roseus [L] G. Don, Dendrophtoe petandra L., Curcuma mangga Val. extracts on T47D cancer cell line. Int Res J Biochem Bioinform. 2011; 1: 22-8, article.

Arung ET, Kusuma IW, Purwatiningsih S, Roh SS, Yang CH, Jeon S, et al. Antioxidant activity and cytotoxicity of the traditional Indonesian medicine Tahongai (Kleinhovia hospita L.) extract. J Acupunct Meridian Stud. 2009; 2: 306-8, CrossRef.

Sandra F, Hendarmin L, Nakao Y, Nakamura N, Nakamura S. TRAIL cleaves caspase-8, -9 and -3 of AM-1 cells: a possible pathway for TRAIL to induce apoptosis in ameloblastoma. Tumour Biol. 2005; 26: 258-64, CrossRef.

Arung ET, Wicaksono BD, Handoko YA, Kusuma IW, Shimizu K, Yulia D, et al. Cytotoxic effect of artocarpin on T47D cells. J Nat Med. 2010; 64: 423-9, CrossRef.

Ji ZQ, Huang XE, Wu XY, Liu J, Wang L, Tang JH. Safety of Brucea javanica and cantharidin combined with chemotherapy for treatment of NSCLC patients. Asian Pac J Cancer Prev. 2014; 15: 8603-5, CrossRef.

Liu J, Huang XE, Tian GY, Cao J, Lu YY, Wu XY, et al. Phase II study on safety and eficacy of Yadanzi® (Javanica oil emulsion injection) combined with chemotherapy for patients with gastric cancer. Asian Pac J Cancer Prev. 2013; 14: 2009-12, CrossRef.

Lu YY, Huang XE, Cao J, Xu X, Wu XY, Liu J, et al. Phase II study on Javanica oil emulsion injection (Yadanzi®) combined with chemotherapy in treating patients with advanced lung adenocarcinoma. Asian Pac J Cancer Prev. 2013; 14: 4791-4, CrossRef.

Nie YL, Liu KX, Mao XY, Li YL, Li J, Zhang MM. Effect of injection of brucea javanica oil emulsion plus chemoradiotherapy for lung cancer: a review of clinical evidence. J Evid Based Med. 2012; 5: 216-25, CrossRef.




DOI: https://doi.org/10.18585/inabj.v7i2.76

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