Dugganaboyana Guru Kumar et al. / Journal of Pharmacy Research 2010, 3(12),3028-3031
Available online through www.jpronline.info Anticancer activity of Cassia senna (L) against prostate carcinogenesis
Research Article ISSN: 0974-6943
Dugganaboyana Guru Kumar1 , Muthaiyan Ahalliya Rathi1 , Periasamy Meenakshi1 , Lakshmanan Thirumoorthi2 , Martin Sunitha2 , Velliyur Kanniappan Gopalakrishnan1, 2* 1
Department of Biochemistry, Karpagam Arts and Science College, Coimbatore-641021, Tamil Nadu, India . 2 Department of Biochemistry, Karpagam University, Coimbatore-641021, Tamil Nadu, India
Received on: 15-06-2010; Revised on: 18-08-2010; Accepted on:13-09-2010 ABSTRACT Prostate cancer (PC) is the most common male non-cutaneous malignancy in Western countries. Since prostate cancer development involves a combination of genetic predisposition and promotional mechanisms, especially the metabolic conversion of testosterone to 5α dihydrotestosterone (DHT) by 5 α reductase. In the present study antitumor activity of ethanolic extract of Cassia senna (150mg/kg body weight, for a duration of 4 months) was evaluated against testosterone and N-Methyl N-Nitroso Urea (MNU).Biochemical estimations including Prostatic acid phosphatase, Lipid peroxidation, enzymic antioxidants and non enzymic antioxidants activity done in the prostate and seminal vesicle tissue homogenate were restored after treatment with ethanolic extract of C.senna. Histopathological Examination Showed significant changes like hyperplastic prostatic acini and malignant proliferation of ductal epithelial cells in the prostate and seminal vesicle of Carcinogen induced rats. After treatment with C.senna extract normal and flow dilated ducts and acini with regular epithelial lining were observed in prostate and partially hyperplastic and partially flattered epithelium in seminal vesicle were observed. In conclusion from these findings it is reported that the ethanolic extract of C.senna has good Suppression of Prostate tumor growth in in vivo model using Testosterone and N-methyl N-nitrosourea for induction of prostate carcinogenesis.
Key words: MNU, Testosterone, Cassia senna, prostate carcinogenesis, antioxidants. INTRODUCTION Prostate cancer is one of the main human cancers in the Western world. Cancer of the prostate is the most frequently diagnosed cancer and the second most frequent cause of death due to cancer in males in the USA and many west European countries [1]. In India, prostate cancer ranks in its fifth incidence and 4th in mortality rate [2]. It has been suggested that a change in the testosterone level with advancing age is an important factor in initiation of benign prostatic hyperplasia and prostate carcinogenesis [3]. Despite extensive research, the etiology of prostate cancer is not clearly defined. It is believed to be multifactorial disease involving genetic, hormonal, dietary, age, race, and environmental causes. The mechanisms leading to the initiation and progression of prostate cancer are largely unknown. One of the reasons that the progress has been slow is due to the lack of suitable animal models. Although there are a number of animal carcinogenesis models, they are based on single sex hormone, testosterone, or a combination of testosterone and estrogen [4]. The combination of testosterone and carcinogen N-methyl-N-nitrosourea has the advantage of inducing higher incidence of prostate carcinogenesis in SpragueDawly rats [5]. This particular model has several advantages including the development of hyperplasia to dysplasia and prostatic intra epithelial neoplasia in short term treatments (5 months).
antioxidant activity. These chemicals block various hormone actions and metabolic pathways that are associated with the development of cancer [9]. A dichloromethane extract of the seeds and leaves of Athrixia elata, however, exhibited moderate growth inhibitory, cytostatic and cytotoxic effects against three cancer cell lines, namely TK10 (renal cancer), MCF7 (breast cancer)and UACC62 (melanoma) [10]. Rosmarinus officinalis (rosemary) contains substantial amounts of carnosol and ursolic acid, the potent antioxidants that possess antitumor activity [11]. Cassia senna (L). (Caesalpinaceae) (‘‘senna’’) is an important medicinal plant [12] . It is one of the most widely used herbal laxatives [13]. The medical action of C.senna can be attributed mainly to the anthraquinone glycosides, especially sennosides A and B [14]. Dried leaves and pods of C.senna contain up to 7% sennosides [15]. Therefore the quest for effective anti-cancer drug is an active research field. Efforts, therefore, are being made to identify naturally occurring anticarcinogens, which would prevent, slow/reverse cancer development. Therefore, the chemoprevention study was conducted to evaluate the effect of Cassia senna in prostate carcinogenesis in Wistar rats. MATERIALS AND METHODS
There is no known acceptable measure for prevention of prostate cancer in humans; and therapeutic agents and surgical procedures offer transient benefits [6] . Although significant progress in cancer chemoprevention has been made in other organ sites, the prevention of prostate cancer has received only moderate attention. This is despite the fact that the prostate is an organ where effective chemopreventive regimens could have a dramatic impact on morbidity and mortality [7]. Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for cancer or tumor. The use of medicinal plants in modern medicine for the prevention or treatment of cancer is an important aspect. According to assessment of WHO about 80% of world population depend on medicinal plants for their health care needs, and more than 30% of the pharmaceutical preparations are based on plants [8]. Ellagicacid and a whole range of flavonoids, carotenoids and terpenoids present in Fragaria vesca (strawberries) and Rubus idaeus (raspberries) have been reported to be responsible for
*Corresponding author. Dr. V.K.Gopalakrishnan Professor in Biochemistry,Karpagam University Coimbatore – 641 021,India Ph : 091-0422-2611146 Fax: 091-0422-2611043 E-mail:
[email protected]
Plant Collection and Extract preparation The leaves of Cassia senna was collected from Pollachi, Tamil Nadu, India. It was authenticated by Dr. G.V.S. Murthy, Botanical Survey of India, Tamil Nadu Agricultural University Campus, Coimbatore, Tamil Nadu, India. A Voucher specimen was deposited in the laboratory for future reference (BSI/SC/5/23/0910/Tech-238). The powdered leaves of C.senna (100 g) was extracted with 500 ml of 95% ethanol. Chemicals Testosterone was purchased from SD Fine Chemicals, Mumbai, MNU (N-Methyl N-Nitroso Urea) was purchased from Sigma U.S.A. and Propylene glycol was purchased from Qualigens Fine Chemicals, Mumbai. Preliminary Phytochemical Screening The phytochemical screening of C.senna was performed as per procedure[16], [17]. Animals Used The Wistar strain of male albino rats weighing between 160-180 g were used in the present study. The animals were housed in large spacious cages and they were given food and water ad libitum during the course of the experiment. The study
Journal of Pharmacy Research Vol.3.Issue 12. December 2010
3028-3031
Dugganaboyana Guru Kumar et al. / Journal of Pharmacy Research 2010, 3(12),3028-3031
Biochemical estimations done in the rat prostate gland and seminal vesicle After the treatment period the rats were sacrificed under chloroform anesthesia, prostate was removed from the adhering connective tissue, washed several times with physiological saline, weight accurately and used for biochemical estimations. The levels of Prostatic acid phosphatase [18], enzymic antioxidant such as SOD [19], Catalase [20] and GPx [21] and Non enzymic antioxidants such as Vitamin C [22] and reduced glutathione [23]. Histological Observations A part of the separated lobes of Prostate gland and Seminal vesicle were fixed in 10% neutral buffered formalin. After fixation, the lobes were embedded in paraffin stained for histopathological observation. It was carried out at vaishnavi histopathology Lab, Chennai. Statistical Analysis The values were expressed as mean ± SD. The statistical analysis was carried out by oneway analysis of variance using SPSS (version 10) statistical analysis program. Statistical significance was considered at p
