Anticancer mechanisms of Strobilanthes crispa Blume hexane extract on liver and breast cancer cell lines

Koh,Rhun  Yian; Lim,Foong  Ping; Ling,Leslie  Siing Yie; Ng,Catherine  Pei Ling; Liew,Siew  Foong; Yew,Mei  Yeng; Tiong,Yee  Lian; Ling,Anna  Pick Kiong; Chye,Soi  Moi; Ng,Khuen  Yen

doi:10.3892/ol.2017.6821

Anticancer mechanisms of Strobilanthes crispa Blume hexane extract on liver and breast cancer cell lines

Authors:
- Rhun Yian Koh
- Foong Ping Lim
- Leslie Siing Yie Ling
- Catherine Pei Ling Ng
- Siew Foong Liew
- Mei Yeng Yew
- Yee Lian Tiong
- Anna Pick Kiong Ling
- Soi Moi Chye
- Khuen Yen Ng
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Affiliations: Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia, Pharmacy Program, School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia, Biomedical Science Program, School of Health Sciences, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500 Selangor, Malaysia, School of Postgraduate Studies and Research, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia
Published online on: August 24, 2017 https://doi.org/10.3892/ol.2017.6821
Pages: 4957-4964

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Abstract

Cancer is a major public health concern not only in developed countries, but also in developing countries. It is one of the leading causes of mortality worldwide. However, current treatments may cause severe side effects and harm. Therefore, recent research has been focused on identifying alternative therapeutic agents extracted from plant‑based sources in order to develop novel treatment options for cancer. Strobilanthes crispa Blume is a plant native to countries including Madagascar and Indonesia. It has been used as an anti‑diabetic, diuretic and laxative in traditional folk medicine. Furthermore, S. crispa has potential in treating cancer, as evidenced in previous studies. In the present study, the cytotoxic and apoptotic activities of S. crispa crude extracts were investigated in liver and breast cancer cell lines. Hexane, ethyl acetate, chloroform, methanol and water extracts prepared from the leaves, and stems of S. crispa were evaluated for their cytotoxicity on HepG‑2 and MDA‑MB‑231 cells using an MTT assay. The anti‑proliferative properties of stem hexane (SH) extract on both cell lines were analysed using cell doubling time determination and cell cycle analysis, while the apoptogenic properties was determined through the detection of caspase‑8. Among the extracts tested, SH extract exhibited the lowest half maximal inhibitory concentrations in both the cell lines. The SH extract induced morphological changes in HepG‑2 and MDA‑MB‑231 cells, and significantly delayed cell population doubling time. Furthermore, it altered cell cycle profile and significantly increased caspase‑8 activity in HepG‑2 cells, but not in MDA‑MB‑231 cells. In conclusion, the SH extract of S. crispa possesses potent anticancer properties and may be a suitable chemotherapeutic target.

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1	Sunilson AJ, Rejitha G, Anandarajagopal K, Das A, Muthappan M and Promwichit P: Cytotoxic effect of Cayratia carnosa leaves on human breast cancer cell lines. Int J Cancer Res. 5:115–122. 2009. View Article : Google Scholar
2	Perz JF, Armstrong GL, Farrington LA, Hutin YJ and Bell BP: The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 45:529–538. 2006. View Article : Google Scholar : PubMed/NCBI
3	El-Serag HB: Epidemiology of hepatocellular carcinoma in USA. Hepatol Res. 37 Suppl 2:S88–S94. 2007. View Article : Google Scholar : PubMed/NCBI
4	Röcken C and Carl-McGrath S: Pathology and pathogenesis of hepatocellular carcinoma. Dig Dis. 19:269–278. 2001. View Article : Google Scholar : PubMed/NCBI
5	Sezgin C: Arsenic trioxide has additive cytotoxic effects on MCF-7 breast cancer cell line with taxanes. Turkish J Med Sci. 32:439–444. 2002.
6	Park S, Bae J, Nam BH and Yoo KY: Aetiology of cancer in Asia. Asian Pac J Cancer Prev. 9:371–380. 2008.PubMed/NCBI
7	Ziegler RG, Anderson WF and Gail MH: Increasing breast cancer incidence in China: The numbers add up. J Natl Cancer Inst. 100:1339–1341. 2008. View Article : Google Scholar : PubMed/NCBI
8	Kelsey JL and Bernstein L: Epidemiology and prevention of breast cancer. Annu Rev Public Health. 17:47–67. 1996. View Article : Google Scholar : PubMed/NCBI
9	Kelsey JL, Gammon MD and John EM: Reproductive factors and breast cancer. Epidemiol Rev. 15:36–47. 1993. View Article : Google Scholar : PubMed/NCBI
10	Hulka BS and Stark AT: Breast cancer: Cause and prevention. Lancet. 346:883–887. 1995. View Article : Google Scholar : PubMed/NCBI
11	Wang S, Liu Q, Zhang Y, Liu K, Yu P, Liu K, Luan J, Duan H, Lu Z, Wang F, et al: Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action. Mol Cancer. 8:812009. View Article : Google Scholar : PubMed/NCBI
12	Beer TM and Bubalo JS: Complications of chemotherapy for prostate cancer. Semin Urol Oncol. 19:222–230. 2001.PubMed/NCBI
13	Leonard RC, Williams S, Tulpule A, Levine AM and Oliveros S: Improving the therapeutic index of anthracycline chemotherapy: Focus on liposomal doxorubicin (Myocet). Breast. 18:218–224. 2009. View Article : Google Scholar : PubMed/NCBI
14	Wonders KY and Reigle BS: Trastuzumab and doxorubicin-related cardiotoxicity and the cardioprotective role of exercise. Integr Cancer Ther. 8:17–21. 2009. View Article : Google Scholar : PubMed/NCBI
15	Goldstein MS: Complementary and Alternative Medicine. J Psychosoc Oncol. 21:1–212. 2003. View Article : Google Scholar
16	Chan LL, George S, Ahmad I, Gosangari SL, Abbasi A, Cunningham BT and Watkin KL: Cytotoxicity effects of Amoora rohituka and chittagonga on breast and pancreatic cancer cells. Evid Based Complement Alternat Med. 2011:8606052011. View Article : Google Scholar : PubMed/NCBI
17	Sunarto PA: Materia Medica Indonesia1st. Penerbitan Directorat Jenderal Pengawasan Obat dan Makanan. Jakarta: pp. 95–99. 1977
18	Burkill I, Birtwistle W, Foxworthy F, Scrivenor J and Watson J: A dictionary of the economic products of the Malay Peninsula1st. Published on behalf of the governments of the Straits settlements and Federated Malay states by the Crown agents for the colonies. London: pp. 2086–2087. 1935
19	Bakar Abu MF, Teh AH, Rahmat A, Othman F, Hashim N and Fakurazi S: Antiproliferative properties and antioxidant activity of various types of Strobilanthes crispus tea. Int J Cancer Res. 2:152–158. 2006. View Article : Google Scholar
20	Ismail M, Manickam E, Danial AM, Rahmat A and Yahaya A: Chemical composition and antioxidant activity of Strobilanthes crispus leaf extract. J Nutr Biochem. 11:536–542. 2000. View Article : Google Scholar : PubMed/NCBI
21	Asmah R, Susi E, Patimah I, Yap Taufiq YH and Fadzelly Mohd AB: Chemical constituents, antioxidant activity and cytotoxic effects of essential oil from Strobilanthes crispus and Lawsonia inermis. J Biol Sci. 6:1005–1010. 2006. View Article : Google Scholar
22	Asmah R, Susi E, Abdah MA, Patimah I, Yap Taufiq YH and Fadzelly Mohd AB: Anticarcinogenic properties of Strobilanthes crispus extracts and its compounds in vitro. Int J Cancer Res. 2:47–49. 2006. View Article : Google Scholar
23	Susi E, Asmah R, Patimah I and Taufiq-Yap YH: Comparing of the cytotoxicity properties and mechanism of Lawsonia inermis and Strobilanthes crispus extract against several cancer cell lines. J Med Sci. 7:1098–1102. 2007. View Article : Google Scholar
24	Yaacob NS, Hamzah N, Kamal Nik Mohamed NN, Abidin Zainal SA, Lai CS, Navaratnam V and Norazmi MN: Anticancer activity of a sub-fraction of dichloromethane extract of Strobilanthes crispus on human breast and prostate cancer cells in vitro. BMC Complement Altern Med. 10:422010. View Article : Google Scholar : PubMed/NCBI
25	Koh RY, Sim YC, Toh HJ, Liam LK, Ong RS, Yew MY, Tiong YL, Ling AP, Chye SM and Ng KY: Cytotoxic and apoptogenic effects of Strobilanthes crispa Blume extracts on nasopharyngeal cancer cells. Mol Med Rep. 12:6293–6299. 2015. View Article : Google Scholar : PubMed/NCBI
26	Mahavorasirikul W, Viyanant V, Chaijaroenkul W, Itharat A and Na-Bangchang K: Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro. BMC Complement Altern Med. 10:552010. View Article : Google Scholar : PubMed/NCBI
27	Schoene NW and Kamara KS: Population doubling time, phosphatase activity, and hydrogen peroxide generation in Jurkat cells. Free Radic Biol Med. 27:364–369. 1999. View Article : Google Scholar : PubMed/NCBI
28	Jemal A, Siegel R, Ward E, Murray T, Xu J and Thun MJ: Cancer statistics, 2007. CA Cancer J Clin. 57:43–66. 2007. View Article : Google Scholar : PubMed/NCBI
29	Chong HZ, Rahmat A, Yeap SK, Akim Md A, Alitheen NB, Othman F and Gwendoline-Ee CL: In vitro cytotoxicity of Strobilanthes crispus ethanol extract on hormone dependent human breast adenocarcinoma MCF-7 cell. BMC Complement Altern Med. 12:352012. View Article : Google Scholar : PubMed/NCBI
30	Chinkwo KA: Sutherlandia frutescens extracts can induce apoptosis in cultured carcinoma cells. J Ethnopharmacol. 98:163–170. 2005. View Article : Google Scholar : PubMed/NCBI
31	Wink M: Functions in plants secondary metabolites and their exploration in biotechnology. Sheffield Academic Press; United Kingdom: pp. 188–2731. 1999
32	Ahmad A, Alkarkhi AFM, Hena S and Khim LH: Extraction, separation and identification of chemical ingredients of Elephantopus Scaber L. using factorial design of experiment. Int J Chem. 1:2009. View Article : Google Scholar
33	Ahmed Y, Rahman S, Akhtar P, Islam F, Rahman M and Yaakob Z: Isolation of steroids from n-hexane extract of the leaves of Saurauia roxburghii. Int Food Res J. 20:2939–2943. 2013.
34	Saludes JP, Garson MJ, Franzblau SG and Aguinaldo AM: Antitubercular constituents from the hexane fraction of Morinda citrifolia Linn. (Rubiaceae). Phytother Res. 16:683–685. 2002. View Article : Google Scholar : PubMed/NCBI
35	Panal S, Urip H, Pandapotan M and Tonel B: Isolation of β-sitosterol from n-hexane extract of Picria fel-terrae Lour. leave and study of its antidiabetic effect in alloxan induced diabetic mice. Int J PharmTech Res. 6:137–141. 2014.
36	Saiin C, Rattanajak R, Kamchonwongpaisan S, Ingkaninan K, Sukontason K, Baramee A and Sirithunyalug B: Isolation and in vitro antimalarial activity of hexane extract from Thai Picrasma javanica B1 stembark. Southeast Asian J Trop Med Public Health. 34 Suppl 2:S51–S55. 2003.
37	Kabashima H, Miura N, Shimizu M, Shinoda W, Wang X, Wang Z, Takahashi S, Harada T, Maruyama H, Tashiro S, et al: Preventive impact of alkaloids with anti-cancer effect extracted from natural herb and the derivatives. WebmedCentral Prev Med. 1:WMC005192010.
38	Lu JJ, Bao JL, Chen XP, Huang M and Wang YT: Alkaloids isolated from natural herbs as the anticancer agents. Evid Based Complement Alternat Med. 2012:4850422012. View Article : Google Scholar : PubMed/NCBI
39	Marzouk MS, Moharram FA, Mohamed MA, Gamal-Eldeen AM and Aboutabl EA: Anticancer and antioxidant tannins from Pimenta dioica leaves. Z Naturforsch C. 62:526–536. 2007. View Article : Google Scholar : PubMed/NCBI
40	de Melo Gomes J, de Sousa Araújo TA, de Almeida e Castro Thijan Nobre V, de Vasconcelos Cabral Lyra D, do Desterro Rodrigues M, do Nascimento Carneiro S, de Amorim Cavalcanti EL and de Albuquerque UP: Antiproliferative activity, antioxidant capacity and tannin content in plants of semi-arid northeastern Brazil. Molecules. 15:8534–8542. 2010. View Article : Google Scholar : PubMed/NCBI
41	Khanna A, Walker GR, Livingstone AS, Arheart KL, Rocha-Lima C and Koniaris LG: Is adjuvant 5-FU-based chemoradiotherapy for resectable pancreatic adenocarcinoma beneficial? A meta-analysis of an unanswered question. J Gastrointest Surg. 10:689–697. 2006. View Article : Google Scholar : PubMed/NCBI
42	Kurt E, Kurt M, Kanat O, Cetintas SK, Aygun S, Palazoglu T, Ozkan L, Evrensel T, Kaya E and Manavoglu O: Phase II study of induction chemotherapy with gemcitabine plus 5-fluorouracil followed by gemcitabine-based concurrent chemoradiotherapy for unresectable locally advanced pancreatic cancer. Tumori. 92:481–486. 2006.PubMed/NCBI
43	Widakowich C, de Castro G Jr, de Azambuja E, Dinh P and Awada A: Review: Side effects of approved molecular targeted therapies in solid cancers. Oncologist. 12:1443–1455. 2007. View Article : Google Scholar : PubMed/NCBI
44	Huggins DJ, Sherman W and Tidor B: Rational approaches to improving selectivity in drug design. J Med Chem. 55:1424–1444. 2012. View Article : Google Scholar : PubMed/NCBI
45	Kawasaki Y and Freire E: Finding a better path to drug selectivity. Drug Discov Today. 16:985–990. 2011. View Article : Google Scholar : PubMed/NCBI
46	Landmark CJ and Johannessen SI: Modifications of antiepileptic drugs for improved tolerability and efficacy. Perspect Medicin Chem. 2:21–39. 2008.PubMed/NCBI
47	Kerr JF, Wyllie AH and Currie AR: Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 26:239–257. 1972. View Article : Google Scholar : PubMed/NCBI
48	Syam S, Abdul AB, Sukari MA, Mohan S, Abdelwahab SI and Wah TS: The growth suppressing effects of girinimbine on HepG2 involve induction of apoptosis and cell cycle arrest. Molecules. 16:7155–7170. 2011. View Article : Google Scholar : PubMed/NCBI
49	Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol. 35:495–516. 2007. View Article : Google Scholar : PubMed/NCBI
50	Sun SY, Hail N Jr and Lotan R: Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst. 96:662–672. 2004. View Article : Google Scholar : PubMed/NCBI
51	Wong RS: Apoptosis in cancer: From pathogenesis to treatment. J Exp Clin Cancer Res. 30:872011. View Article : Google Scholar : PubMed/NCBI
52	Hassan M, Watari H, AbuAlmaaty A, Ohba Y and Sakuragi N: Apoptosis and molecular targeting therapy in cancer. Biomed Res Int. 2014:1508452014. View Article : Google Scholar : PubMed/NCBI
53	Hengartner MO: The biochemistry of apoptosis. Nature. 407:770–776. 2000. View Article : Google Scholar : PubMed/NCBI
54	Cullen SP and Martin SJ: Caspase activation pathways: Some recent progress. Cell Death Differ. 16:935–938. 2009. View Article : Google Scholar : PubMed/NCBI
55	Shiu RP, Watson PH and Dubik D: c-myc oncogene expression in estrogen-dependent and -independent breast cancer. Clin Chem. 39:353–355. 1993.PubMed/NCBI
56	Shen Y and White E: p53-dependent apoptosis pathways. Adv Cancer Res. 82:55–84. 2001. View Article : Google Scholar : PubMed/NCBI
57	Zhang L and Fang B: Mechanisms of resistance to TRAIL-induced apoptosis in cancer. Cancer Gene Ther. 12:228–237. 2005. View Article : Google Scholar : PubMed/NCBI
58	Ramadan S, Terrinoni A, Catani MV, Sayan AE, Knight RA, Mueller M, Krammer PH, Melino G and Candi E: p73 induces apoptosis by different mechanisms. Biochem Biophys Res Commun. 331:713–717. 2005. View Article : Google Scholar : PubMed/NCBI