Anticancer and Apoptosis Induction Properties of Apium Graveolens Seeds
Abstract:
Based on traditional medicinal
use Apium graveolens seed was
selected to evaluate its anti-cancer property with special reference to
apoptosis induction, if any. When the water, alcohol and hexane extracts of the
dried powder of the plant seeds were tested for cytotoxicity to Dalton’s
Lymphoma Acitic (DLA) cells in vitro
using Tryphan blue method, only the n-hexane extract showed significant
activity at 500 µg/ml level. The extract induced apoptosis as evidenced by
morphological changes. The cytotoxicity of this extract was found to be more to
cancer cells (DLA) compared to normal cells (thymocytes and macrophages). An
active chloroform fraction was separated from this extract. The active fraction
at a dose of 200 mg/kg protected 75 % of the mice challenged with 1 X 106 DLA
cells whereas all untreated control mice died of cancer. Thin Layer
Chromatography (TLC) on silica gel further separated this anticancer fraction
into 2 cytotoxic components. One of them was identified as a steroid positive
component whereas the other was an alkaloid positive component. The steroid
component induced apoptotic cell death while the other component induced
necrotic cell death. These components are attractive materials for further
studies leading to possible anti-cancer drug development.
References:
[1]. Pushpangadan P,
Subramoniam A. Pharmacological investigations on Indian medicinal plants: a
search for anti-cancer agents. Amala Research Bulletin 1998: 18:123-129
[2]. Subramoniam A.
Defining molecular targets in the discovery of phytomedicines for cancer. Amala
Res Bull 2001: 2: 82-87.
[3]. Bertram JS.
Cancer prevention by carotenoids. Mechanistic studies in cultured cells. Ann N
Y Acad Sci 1993: 691: 177-191.
[4]. Blot WJ, Li J-Y,
Taylor PR, et al. Nutrition intervention trials in Linxin, China:
Supplementation with specific vitamin/mineral combinations, cancer incidence,
and disease specific mortality in the general population. J Natl Cancer Inst
1995: 85: 1483- 1492.
[5]. Menon LG, Kuttan
R, Kuttan G. Inhibition of lung metastasis in mice induced by B16F-10 melanoma
cells by polyphenolic compounds. Cancer Lett 1995: 95: 221-225.
[6]. Cardile V, Scifo
C, Russo A, Falsaperla M, Morgia G, Motta M, Renis M, Imbriani E, Silvestre G.
Involvement of HSP70 in resveratrol-induced apoptosis of human prostate cancer.
Anticancer Res. 2003: 23: 4921-4926.
[7]. Crowell PL.
Prevention and therapy of cancer by dietary monoterpenes. J Nutr 1999: 129:
775S-778S.
[8]. Jose JK, Joy KL,
Kuttan R. Effect of Emblica officinalis, Phyllanthus amarus and Picrorrhiza
kurroa on N-nitrosodiethylamine induced hepatocellular carcinogenesis.
Cancer Letter 1999: 135: 1-6.
[9]. Joy KL, Kumar NV,
Kuttan G, Kuttan R. Effect of Picrorrhiza kurroa extract on transplanted
tumors and chemical carcinogenesis in mice. J Ethnopharmacol. 2000: 71:
261-267.
[10]. Subramoniam A,
Rajasekharan S, Latha PG, Evans DA and Pushpangadan P. Immunomodulatory and
anti-tumor activities of Janakia arayalpathra. Fitoterapia 1996: 57:
140-144.
[11]. Subramoniam A.
Role of cis unsaturated fatty acids in cell growth regulation. Amala Res Bull
1997:17: 27-31.
[12]. Subramoniam A,
Rajasekharan S, Pushpangadan P, George V, Nair SG. A process to prepare an
herbal formulation for cancer from Janakia arayalpathra root and Trichopus
zeylanicus leaf. Inventors (Chennai/2001). Patent No: MAS/659/01(Patent
obtained).
[13]. Mehta RG,
Pezzuto, JM. Discovery of cancer preventive agents from natural products: From
plants to prevention. Curr Oncol Rep 2002: 4: 478-486.
[14]. Shylesh BS,
Ajikumaran Nair S, Subramoniam A. Induction of cell specific apoptosis and
protection from Daltons’ Lymphoma challenge in mice by Emilia sonchifolia (active
fraction) containing a terpene, active principle. Indian J Pharmacol 2005:
37:232-237.
[15]. Subramoniam, A,
Subhisha S, Ajikumaran Nair S, Shylesh BS, Nair G.M. Bryophytes of Kerala: a
potential source of anti-cancer agents. Amla Res. Bull.2003: 23: 78-83
[16]. Hanahan D,
Weinberg RA. Resistance to apoptosis and cancer. Cell, 2000: 100: 57- 70.
[17]. Martin Z,
Anne-Odile H, Wiebke B, Gerard E. Apoptosis regulators and their role in
tumorigenesis. Biochem Biophys Acta, 2001: 1551:F1-F37.
[18]. Green DR,
Kroemer G. The pathophysiology of mitochondrial cell death. Science, 2004: 305:
626-629.
[19]. Subramoniam A.,
Ajikumaran Nair S. Application of apoptosis in the search for plant-derived
chemopreventive/therapeutic agents. Amala Research Bulletin, 2004: 24: 1-11.
[20]. Shaik Imam,
Hussain SJ. Some important herbs used in the treatment of cancer: part-1. In:
Role of biotechnology in medicinal and aromatic plants. I A Khan & A Khanum
(eds) 2004: Volume 11, 1-50. Ukaaz Publications, Hyderabad.
[21]. Choochote W,
Tuetun B, Kanjanapothi D, Rattanachanpichai E, Chaithong U, Chaiwong P,
Jitpakdi A, Tippawangkosol P, Riyong D, Pitasawat B. Potential of crude seed
extract of celery, Apium graveolens L., against the mosquito Aedes
aegypti (L.) (Diptera:Culicidae). J Vector Ecol. 2004: 29: 340-346.
[22]. Seetharami Reddi
TVV, Prasanthi S and Ramarao Naidu BVA. Medicinal and aromatic plants of India.
In: Role of biotechnology in medicinal and aromatic plants. I A Khan & A
Khanum (eds) 2005: Volume12,1-146. Ukaaz Publications, Hyderabad.
[23]. Mary KT, Kuttan
G, Kuttan R. Partial purification of tumour reducing principles from Helianthes
elastica. Cancer Lett. 1994: 81: 53-56.
[24]. Wagner H, Bladt
S, Zgainski EM. Plant drug analysis. Berlin, Heidelberg, New York, Tokyo;
Springer-Verlag, 1984.