Anticancer and immunostimulatory compounds from Andrographis paniculata

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Abstract

Andrographis paniculata extract is traditionally used as a medicine to treat different diseases in India, China and Southeast Asia. In the present study, we evaluated the anticancer and immunomodulatory activity of the methanolic extract of Andrographis paniculata in human cancer and immune cells. The methanolic extract of Andrographis paniculata was fractionated into dichloromethane, petroleum ether and aqueous extracts and screened for bioactivity. Our results indicate that the dichloromethane fraction of the methanolic extract retains the active compounds contributing for both the anticancer and immunostimulatory activity. Dichloromethane fraction significantly inhibits the proliferation of HT-29 (colon cancer) cells and augments the proliferation human peripheral blood lymphocytes (HPBLs) at low concentrations. On further fractionation of the dichloromethane extract we could isolate three diterpene compounds, i.e. [1] andrographolide, [2] 14-deoxyandrographolide and [3] 14-deoxy-11,12-didehydroandrographolide. Andrographolide showed anticancer activity on diverse cancer cells representing different types of human cancers. Whereas all the three molecules showed enhanced proliferation and interleukin-2 (IL-2) induction in HPBLs.

Introduction

In recent years focus on use of non-traditional approaches to treat diseases has been revived all over the world. The evidence collected till now shows immense potential of medicinal plants used in traditional systems (Hoareau et al., 1999). The use of herbal extracts and nutritional supplements either as alternative or complimentary medicine to the conventional chemotherapy for treatment of cancer is well documented in Ayurveda which is an alternative medical system that has been practiced primarily in the Indian subcontinent for 5000 years (Dahanukar et al., 2000). Andrographis paniculata (Acanthaceae), also known commonly as “kalmegh,” is a well known medicinal plant of Ayurveda and has been used for centuries in Asia. About 26 different polyherbal formulations of this plant are mentioned in Ayurveda as a popular remedy for the treatment of various disorders. Andrographis paniculata is an annual shurb grows abundantly in India and cultivated extensively in China and Thailand. The aerial parts of the plant (leaves and stems) are used to extract the active phytochemicals. The plant extract is known to contain diterpenes, flavonoids and stigmasterols (Siripong et al., 1992). Extensive research of the last few decades has revealed that the herbal extract is useful as an anti-inflammatory (Shen et al., 2002), antiviral (Chang et al., 1991, Calabrese et al., 2000), antithrombotic (Zhao and Fang, 1991), anticancer (Matsuda et al., 1994), immunostimulatory (Puri et al., 1993, See et al., 2002), hypoglycaemic (Zhang and Tan, 2000) and hypotensive agent (Zhang and Tan, 1996).

Andrographolide, the major diterpenoid of the Andrographis paniculata extract has shown cytotoxic activity against KB (human epidermoid carcinoma) and P388 (lymphocytic leukaemia) (Siripong et al., 1992) cells. The methanol extract of aerial parts of Andrographis paniculata and some of the isolated compounds showed growth inhibitory and differentiating activity on M1 (mouse myeloid leukaemia) cells (Matsuda et al., 1994). The ethyl alcohol extract and purified diterpene andrographolides are reported to stimulate both antigen specific and non specific immune responses in mice (Puri et al., 1993). However, no systematic study has been reported addressing the immunostimulatory activity of Andrographis paniculata extract in human immune cells. Here we report the immunomodualtory activities of Andrographis paniculata extract and its components in human immune cells and anticancer activity in human cancer cells.

Section snippets

Cell lines

Human cancer cell lines SW620 and A498 were purchased from the American Type Culture Collection, Manassas, VA, USA. NCI/ADR-RES, U251, HT29, H522, M14, SKOV3 and DU145 were purchased from the National Cancer Institute, Bethesda, USA. All cells were maintained in RPMI 1640 supplemented with penicillin (100 units/ml), streptomycin (100 mg/ml) and 10% foetal bovine serum. Cells were incubated at 37 °C in a humidified, 5% CO2 atmosphere.

Reagents

Streptomycin, penicillin G, foetal bovine serum, RPMI 1640,

Results and discussion

Some phytochemicals present in medicinal plants have been reported to possess substantial antioxidant, anti-mutagenic and anti-carcinogenic activities and are being extensively explored for their potential for treatment and prevention of cancer (Kucuk, 2002). The well-known compounds like paclitaxel, a diterpenoid from Taxus brevifolia, and vincristine, an alkaloid from Catharanthus roseus, have been proved as antineoplastic drugs in clinic (Wall and Wani, 1996, Neuss et al., 1975). The aerial

Acknowledgements

We thank Ch. Mahender, T. Srikanth and S. Siva sanjeeva rao for their technical help in this study. We also thank Dr. A. Venkateswarlu and R. Rajagopalan for their interest in the present work.

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