Leukemia Research 34 (2010) 1483–1492 Contents lists available at ScienceDirect Leukemia Research journal homepage: www.elsevier.com/locate/leukres Typhonium flagelliforme inhibits the proliferation of murine leukemia WEHI-3 cells in vitro and induces apoptosis in vivo Syam Mohan a , Ahmad Bustamam Abdul a,b,∗ , Siddig Ibrahim Abdelwahab a , Adel S. Al-Zubairi a,c , Mohamed Aspollah Sukari d , Rasedee Abdullah e , Manal Mohamed Elhassan Taha a , Ng Kuan Beng a , Nurbaity Mohd Isa a a UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Malaysia b Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Malaysia c Department of Clinical Biochemistry, University of Sana’a, Sana’a, Yemen d Department of Chemistry, Faculty of Science, University Putra Malaysia, Serdang, Malaysia e Department of Pathology and Microbiology, Faculty of Veterinary Medicine, University Putra Malaysia, Serdang, Malaysia article info Article history: Received 8 February 2010 Received in revised form 23 April 2010 Accepted 27 April 2010 Available online 1 June 2010 Keywords: Apoptosis BALB/c mice Cytotoxicity Typhonium flagelliforme WEHI-3 leukemia cells abstract Typhonium flagelliforme (TF) is a tropical plant, traditionally used by the ethnic population of Malaysia for the cure of various cancers. This plant had shown to induce antiproliferative effect as well as apoptosis in cancer cells. However, there is no available information to address that TF affects murine leukemia cells in vitro and in vivo. Here, we investigated in vitro and in vivo effects of TF on murine leukemia WEHI-3 cells. It was found that the growth of leukemia cells in vitro was inhibited by the various extracts of TF. Among these fractions, the dichloromethane (DCM) tuber extracts of TF showed the lowest IC 50 (24.0 ± 5.2 g/ml) and had demonstrated apoptogenic effect when observed under fluorescent microscope. We investigated the in vivo effects of DCM tuber extracts of TF on murine leukemia cells, and the results showed that the counts of immature granulocytes and monocytes were significantly decreased in peripheral blood of BALB/c leukemia mice after the oral administration of DCM tuber extracts of TF for 28 days with three doses (200, 400 and 800 mg/kg). These results were confirmed by observing the spleen histopathology and morphology of enlarged spleen and liver in leukemia mice when compared with the control. Furthermore, the cell death mechanism in the spleen tissue of treated mice was found via apoptosis. © 2010 Elsevier Ltd. All rights reserved. 1. Introduction Leukemia is a group of heterogeneous neoplastic disorder of white blood cells characterized by the uncontrolled proliferation and block in differentiation of hematopoietic cells [1]. In Malaysia, leukemia is the commonest cancer occurring in children. The crude incidence rate of pediatric malignancies in Malaysia was 77.4 per million children aged less than 15 years. Among cancer deaths in 1998, leukemia stands at the fourth place of commonest diagnoses [2]. Treatment of leukemia is a multidisciplinary effort. The modal- ities of treatment include radiotherapy, chemotherapy, hormonal therapy, immune therapy and symptomatic and supportive ther- apy. A keen interest in anti-cancer therapy of herbal plants has developed recently. This interest in therapy with drugs of plant origin is due to several reasons; namely, conventional medicine can be inefficient (e.g. side effects and ineffective therapy), abu- ∗ Corresponding author at: UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, 43400 UPM Serdang, Malaysia. Tel.: +60 12 6894693; fax: +60 38 9472101. E-mail address: abustamam@putra.upm.edu.my (A.B. Abdul). sive and/or incorrect use of synthetic drugs results in side effects and other problems, a large percentage of the world’s population does not have access to conventional pharmacological treatment, and folk medicine and ecological awareness suggest that “natural” products are harmless [3]. The plant Typhonium flagelliforme, commonly known as ‘rodent tuber’ in Malaysia, is often used as traditional remedy for alter- native cancer therapies, including leukemia by various ethnic populations [4]. This plant is widely distributed in soft, damp and shady habitats in South-East Asia reaching Northern Australia and South India [5]. TF is now commercially available as a healthcare supplement to cure breast, lung, rectum, liver, prostate, leukemia, pancreas and cervical cancer [6]. There are few in vitro studies that have established the anti-cancer properties of TF on different can- cer cell lines, including lung cancer NCI-H23 [7,8], breast cancer HS578T [5,7], liver cancer Hep-G2, breast cancer T-47D [7] and murine P388 leukemia cells [9]. But till today there is no animal study done to evaluate the anti-cancer pharmacological potency of TF. Nature is an attractive source of new therapeutic candidate as a tremendous chemical diversity is found in millions of species of microorganisms, animals, marine organisms and most notably from 0145-2126/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.leukres.2010.04.023