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Evaluation of the anticancer activities of pomegranate (Punica granatum)

Natural and some synthetic compounds can prevent, suppress, or reverse the progression of cancer. Natural products have proven to be the most effective in terms of their ability to alter the function of proteins relevant to cancer. In the present study, the anticancer potentiality of pomegranate (Punica granatum) and harmal (Rhazya stricta) were assessed.

Different extracts of the two plants were utilized against Colon cancer (CACO) and Hepato-cellular carcinoma (HepGII) cell lines. All studied extracts showed a significant reduction in cell proliferation with dose dependant response. Moreover, all of the studied extracts showed different anti-proliferative profiles regarding extract type and concentrations. However, the Rhza H extract showed the highest cytotoxic effect among allextracts with HepG2 and Caco cells (IC50 25 μg/mℓ and 35 μg/mℓ), respectively.

pomegranate 35RESEARCH TITLE: Evaluation of the anticancer activities of pomegranate (Punica granatum) and harmal (Rhazya stricta) plants grown in Saudi arabia

COUNTRIES: Saudi Arabia, Egypt

CONDUCTED BY: Scientific Research Deanship, Biotechnology Research Unit, Taif University, Kingdom of Saudi Arabia; Department of Genetics, Faculty of Agriculture, Cairo University, Giza, Egypt; Department of Genetics, Faculty of Agriculture and Natural Resources, Aswan University, Egypt.

PUBLISHED ON: International Journal of Current Microbiology and Applied Sciences

RESEARCH:

Abstract

Natural and some synthetic compounds can prevent, suppress, or reverse the progression of cancer. Natural products have proven to be the most effective in terms of their ability to alter the function of proteins relevant to cancer. In the present study, the anticancer potentiality of pomegranate (Punica granatum) and harmal (Rhazya stricta) were assessed. Different extracts of the two plants were utilized against Colon cancer (CACO) and Hepato-cellular carcinoma (HepGII) cell lines. All studied extracts showed a significant reduction in cell proliferation with dose dependant response. Moreover, all of the studied extracts showed different anti-proliferative profiles regarding extract type and concentrations. However, the Rhza H extract showed the highest cytotoxic effect among allextracts with HepG2 and Caco cells (IC50 25 μg/mℓ and 35 μg/mℓ), respectively.

Introduction

Natural products have proven to be the most effective in terms of their ability to alter the function of proteins relevant to cancer (Muhtasib, 2006). Plants have been an important source of medicine for thousands of years. Even today, the World Health Organization estimates that up to 80 % of people still rely mainly on traditional remedies such as herbs for their medicines (Tripathi and Tripathi, 2003; Demiray et al., 2009). Medicinal plants constitute one of the main sources of new pharmaceuticals and healthcare products Medicinal plants have been curing various disorders in human being from the time immemorial. Among the human diseases treated with medicinal plants is cancer (Koduru et al., 2007). Medicinal plants play important role in the development of potent therapeutic agents which developed to new drugs. Plant derived drugs came into use in the modern medicine through the uses of plant material as indigenous cure in folklore or traditional systems of medicine. From 1971 to 1990 new drugs such as ectoposide, E-guggulsterone, teniposide, nabilone, plaunotol, Z-guggulsterone, lectinan, artemisinin and ginkgolides appeared all over the world (Samy and Gopalakrishnakone, 2007). Saudi Arabia has 2028 plant species out of which 300 have different medical applications (Amin and Mousa, 2007). There have been many efforts to detect the anticancer potentialities of some Saudi indigenous plants species that are popular in Saudi traditional medicine. Yassen et al., (2012) published detailed pharmacological screening of 11 medicinal plants from Tabuk region at KSA. Cytotoxic effect of three plants was detected. Almehdar et al (2012) utilized different human cancerous cell lines to evaluate the anticancer activity of forty species of plants traditionally used in Saudi Arabia for the treatment of a variety of diseases. Interesting cytotoxic activity was observed for Hypoestes forskaolii, Withania somnifera, Solanum glabratum, Adenium obesum, Pistacia vera oleoresin, Caralluma quadrangula, Eulophia petersii, Phragmanthera austroarabica, and Asparagus officinalis. The anticancer prosperities of Achillea fragrantissima (Af) was reported by (Alenad et al., 2012) using human chronic myeloid leukemia (CML) (K562), T cell lymphoma (Jurkat) and hepatocellular carcinoma (HepG2) cell lines. Harmal (Rhazya stricta Decne) and Pomegranate (Punica granatum) are two important plants that are used intensively in folkloric medicine to cure various diseases is Saudi Arabia. R. stricta is an important medicinal plant widely distributed in Saudi Arabia, South Asia and the Middle East. It is a member of the Apocynaceae family (Gilani et al., 2007; Baeshen et al., 2012). It possesses anti-oxidant, anti-carcinogenic and free radical scavenging properties (ElKady 2013). Four indole alkaloids were isolated from Rhazya stricta leaves and roots by Mukhopadhyay et al (1981). Three of these isolated are vallesiachotamine, sewarine and tetrahydrosecamine displayed cytotoxic activity. Pomegranate (Punica granatum) is one of the Kingdom’s most indemand fruits. Al-Baha and Taif are both well-known for farming this fruit, but Taif’s pomegranate supply remains the most popular. The potential anticancer activity of Rhazya stricta against human breast cancer cells in vitro was confirmed by Baeshan and his coworkers (2012). They found that, the ethanol extract of Rhazya stricta potently inhibited cellular growth and colony formation of human breast cancer cell lines, MCF-7 and MDA-MB-231, in a dose- and time-dependent manner. Furthermore, it induced sequences of events marked by apoptosis, accompanied by a loss of cell viability, chromatin condensation, DNA fragmentation and proteolytic cleavage of poly (ADP-ribose) polymerase. In addition, the anticancer potentiality of Rhazya stricta aginest non-small lung cancer cell line A549 was explored by ElKady (2013) at different cellular and molecular levels. The suppuration of cell growth was observed which was correlated with apoptosis. However, no reports deals with the anticancer potentiality of Rhazya stricta against lung or colon cancer have been published. From the other hands, there are several lines of evidences for the anticancer activity of pomegranate. Several studies have been conducted to evaluate the anticancer activity of pomegranate against different types of cancer such as colon and breast cancer (Abdel Motaal and Shaker, 2011); breast cancer (Banerjee and Talcott, 2012); prostate cancer (Lansky et al., 2005); lung , breast and cervical cancer (Aqil et al., 2012). So far, no studies have been conducted to evaluate the anticancer properties of Saudi pomegranate cultivars. Accordingly, the aim of the present work is to investigate, evaluate and compare the anticancer activity of Saudi Rhazya stricta and pomegranate cultivars against colon and hepatocellular carcinoma cell lines.

In the present study, we applied the MTT test to evaluate the biosafety of cytotoxic effect of different Rhza strecta and pomegranate extracts HepG2 and Caco cell lines. Therefore, cancer and normal cells were exposed to increasing concentrations (10-100 µg /ml of culture medium) of the tested extracts. The MTT assays data are presented respectively in Tables (4-7) All studied extracts produced a reduction in cell proliferation. The obtained results show dose dependant response. The extracts showed different antiproliferative profiles regarding extract type and concentrations. The Rhza H extract was the highest cytotoxic extracts with HepG2 and Caco cells (IC50 25 μg/mℓ and 35 μg/mℓ) respectively. Nowadays it is well known that natural products not only offer protection against oxidative reaction but also suppress proliferation of cancer cells in culture as well as in vivo (Siriwardhana et al., 2003; Kuete et al., 2009; Choi et al., 2012). There are line of evidence indicating that Medicinal plants constitute a common alternative for cancer prevention and treatment in many countries around the world (Soobrattee et al., 2006; Mehta et al., 2010). The first antitumor drugs from plants with an application in cancer chemotherapy were developed five decades ago. A great achievement in this respect is the elaboration of drugs such as: vinblastine and vincristine (Catharanthus roseus), paclitaxel (Taxus brevifolia), silvestrol (Aglaia foveolata), eliptinium (Bleekeria vitensis) (Cragg and Newman, 2005), chrysin (Passiflora incarnate), artemisinin (Artemisia annua) (Newman and Cragg, 2007). Approximately, 60% of the anticancer drugs currently used have been isolated from natural products from the plants. At this time, more than 3000 plants worldwide have been reported to possess anticancer properties. In the present study, the cytotoxicity of Rhazya stricta and pomegranate for the cancer cells were study and evaluated. All studied extracts produced a reduction in cell proliferation. The obtained results show dose dependant response. The extracts showed different antiproliferative profiles regarding extract type and concentrations. The Rhza H extract was the highest cytotoxic extracts with HepG2 and Caco cells (IC50 25 μg/mℓ and 35 μg/mℓ) respectively. The obtained results were in agreement with different studies that were conducted to evaluate the cytptoxic effect of different pomegranate extracts against different cancerous cell lines (Abdel Motaal and Shaker 2011; Aqil et al., 2012; Yazici et al., 2012; Banerjee et al., 2012). On the other hand, Rhazya stricta showed antitumor effect among the two studied cancerous cell lines. These results in consistence with several studies were carried out to assess the anticancer effect of different Rhazya stricta extracts (Ali et al., 2000; Gilani et al., 2007; Baeshen et al., 2012; Elkady 2013). Several reports described that the anticancer activity of the medicinal plants is may be due to the presence of antioxidants (viz., vitamins, carotene, enzymes, minerals, polysaccharides, polyphenols, flavonoids, lignins, xanthones, etc.). In addition, it was reported that these plants may promote host resistance against infection by re-stabilizing body equilibrium and conditioning the body tissues (G Pandey and S Madhuri). In fact, Harmal and pomegranate were shown to contain several of these antioxidants. Thus, the various combinations of the active components of these plants after isolation and identification can be made and have to be further assessed for their synergistic effects. Preparation of standardized dose and dosage regimen may play a critical role in the remedy of cancer. The rate with which cancer is progressing, it seems to have an urgent and effective effort for making good health of humans as well as animals. There is a broad scope to derive the potent anticancer agents from medicinal plants, which need thorough research. For the best of our knowledge, this is the first study that proves the anticancer activities of Rhazya stricta and pomegranate cultivated in Saudi Arabia against colon and hepatocellular carcinoma cell lines.

YEAR: 2015