Potential of traditional ayurvedic formulation, Triphala, as a novel anticancer drug
Introduction
Naturally occurring phytochemicals are widely used in the traditional Indian medicinal system of Ayurveda for treatment of a variety of diseases. Some of the plant products have shown a remarkable anti-tumor property against various human cancers [1], [2], [3]. However, the detailed mechanisms of action of these phytochemicals at cellular and molecular level have not been fully elucidated [4], [5]. Triphala (TPL) is an herbal formulation consisting of the dried and powdered fruits of three plants, Terminalia chebula, Emblica officinalis and Terminalia bellerica in equal proportions. It is an important medicine of the ‘rasayana’ group and is believed to promote health, immunity and longevity [6]. This formulation, rich in antioxidants, is a frequently used Ayurvedic medicine to treat many diseases such as anemia, jaundice, constipation, asthma, fever and chronic ulcers. Most people practicing Ayurvedic medicine consume TPL as a ‘health tonic’. Recent studies have reported anti-clastogenic and anti-tumor properties of E. officinalis [7], [8] and anti-proliferative effect of T. chebula [9]. However, the anticancer property of TPL has not been reported to the best of our knowledge. This study was, therefore, undertaken to examine the anti-tumor effects of TPL in vitro as well as in vivo. An attempt has been made to investigate the effect of TPL on MCF-7 cell line and on the growth of lymphoma tumor transplanted in Swiss mice. It was found that normal and tumor cells responded differentially to TPL and the treatment of tumor bearing animals with TPL caused substantial regression of tumor growth. These results point to the promise of TPL as a potential anti-tumor drug, which warrants testing in clinic for therapeutic application.
Section snippets
Cell culture and harvesting
Dulbecco's Modified Eagle's Medium (DMEM) was purchased from Gibco Co., USA, F-12 medium, hydrocortisone, fetal bovine serum (FBS) and horse serum were obtained from Himedia, Mumbai, India. MCF-7 and MCF-10 F cells were purchased from National Centre for Cell Science, Pune, India. MCF-7 cells were cultured in DMEM supplemented with FBS (10%) and antibiotics (streptomycin 200 μg/ml and penicillin 100 units/ml) at 37 °C in 5% CO2 environment. Cells were harvested from 80 to 90% confluent culture by
TPL induced cytotoxicity in normal and tumor cells
The effects of TPL on human breast cancer cells (MCF-7), mouse transplantable thymic lymphoma cells (barcl-95), human normal breast cells (MCF-10 F), mouse hepatocytes and splenocytes, and human peripheral blood mononuclear cells were studied using trypan blue dye exclusion method (Fig. 1, Fig. 2). Further, inhibition of proliferation induced by TPL in MCF-7 was studied using MTT assay (Fig. 3). Treatment of MCF-7 and barcl-95 cells with increasing concentrations of TPL resulted in a
Discussion
In the present study we have investigated the cytotoxic effects of TPL on normal and tumor cells of human and mouse origin. TPL showed substantially higher cytotoxicity to tumor cells and significantly lower toxicity towards normal cells as determined by trypan blue staining (Fig. 1). Moreover, the toxicity manifested by TPL in MCF-7 cells was also demonstrated in terms of changes in morphological features (Fig. 2A) as well as by inhibition in cell proliferation by MTT assay (Fig. 3). The
Acknowledgements
T. Sandhya would like to acknowledge the award of DAE fellowship for the course of this work. The authors would also like to acknowledge Ajanta pharmaceuticals and Dr. K.I. Priyadarshini for providing the Triphala powder and Dr. R.C. Chaubey and Mr. H.N. Bhilwade for help in SCGE experiments.
References (21)
- et al.
Curcumin induces apoptosis in human breast cancer cells through p53-dependant BAX induction
Fed. Eur. Biol. Soc. Lett.
(2002) - et al.
The evaluation of the radioprotective effect of Triphala (an Ayurvedic rejuvenating drug) in the mice exposed to radiation
Phytomedicine
(2002) - et al.
Antitumor activity of Emblica officinalis
J. Ethnopharmacol.
(2001) - et al.
Inhibition of cancer cell growth by crude extract and the phenolics of Terminalia chebula retz. fruit
J. Ethnopharmacol.
(2002) Role of adaptation on radiation-induced thymic lymphoma in mice
Mutat. Res.
(1996)- et al.
Gamma ray induced DNA damage in human and mouse leucocytes measured by SCGE-Pro: software developed for automated image analysis and data processing for Comet assay
Mutat. Res.
(2001) - et al.
Curcumin mediated apoptosis in AK-5 tumor cells involves the production of reactive oxygen intermediates
Fed. Eur. Biol. Soc. Lett.
(1999) - et al.
Cytotoxic activity of hydrolysable tannins against human oral tumor cell lines—a possible mechanism
Phytomedicine
(2000) Redox-sensitive mechanisms of phytochemical-mediated inhibition of cancer cell proliferation (Review)
J. Nutr. Biochem.
(2003)- et al.
Stimulation of p38 mitogen-activated protein kinase is an early regulatory event for the cadmium-induced apoptosis in human promonocytic cells
J. Biol. Chem.
(2000)
Cited by (107)
Alzheimer's disease: Molecular aspects and treatment opportunities using herbal drugs
2023, Ageing Research ReviewsNano-ayurvedic medicine and its potential in cancer treatment
2023, Journal of Integrative MedicineIntegrating ayurvedic medicine into cancer research programs part 2: Ayurvedic herbs and research opportunities
2023, Journal of Ayurveda and Integrative MedicineCitation Excerpt :Existing preclinical models are not able to reproduce the full mechanisms of action or potential of these herbs. Often a compound is deemed effective based on cytotoxic or apoptotic effects for tumor cells in culture or in vivo tumors [31]. One approach to understanding potential of Ayurvedic pharma is through “Network Pharmacology”.
Development of triphala churna extract mediated iron oxide nanoparticles as novel treatment strategy for triple negative breast cancer
2022, Journal of Drug Delivery Science and TechnologyCitation Excerpt :It is considered as a general well-being medicine that helps to treat numerous illnesses like iron deficiency, cancer, jaundice, obstruction, asthma, fever, persistent ulcers, ongoing blockage, absorption issues, cardiovascular infection, hypertension sickness, decreased serum cholesterol, helpless liver capacity, internal organ irritation, etc. [13–15]. The Triphala churna (powder) affirms the presence of many valuable phytoconstituents such as gallic acid, ellagic acid, chebulinic acid, l-ascorbic acid, alkaloids, bellaricanin, beta-sitosterol, flavonoids (Quercetin, Luteolin etc), saponins, amino acids and so forth which shows strong antioxidant and anticancer activities [16]. Recently, Triphala has also demonstrated potent anticancer activity in HeLa (cervical adenocarcinoma), PANC-1 (pancreatic adenocarcinoma), and MDA-MB-231 (triple-negative breast carcinoma) cells [17].
Role of herbal bioactives and their formulations in the treatment of gastrointestinal disorders
2022, Herbal Bioactive-Based Drug Delivery Systems: Challenges and Opportunities