COLLECTION AND DATA-MINING OF BIOACTIVE COMPOUNDS WITH CANCER TREATMENT PROPERTIES IN THE PLANTS OF FABACEAE FAMILY

COLLECTION AND DATA-MINING OF BIOACTIVE COMPOUNDS WITH CANCER TREATMENT PROPERTIES IN THE PLANTS OF FABACEAE FAMILY

Balan Velusamy, Saravanan Kaliyaperumal* and Arulpriya Raju

PG & Research Department of Zoology, Nehru Memorial College (Autonomous) Puthanampatti – 621 007, Tiruchirapalli, Tamilnadu, India.

ABSTRACT: Medicinal plants therapeutic agents are a big source of information for a wide variety of chemical constituents which could be developed as new drugs. The present study focused on anticancer, antitumor anticarcinogenic and cancer preventive activities of bioactive compounds found in plants belonging to Fabaceae family. The bioactive compounds and their scientific details were mining from publically available phytochemical databases (Dr. Duke’s phytochemistry and ethnobotanical database and USDA phytochemical database).  Fabaceae family is one of the largest family which includes 18,860 plant species, of them, 12 plant species were identified to posses 106 bioactive compounds related to cancer treatment. The plant species such as Acacia nilotica, Arachis hypogaea, Cajanus cajan, Crotalaria juncea, Glycine max, Mimosa pudica, Pisum sativum, Psoralea esculenta, Tamarindus indica, Trifolium pratense, Trigonella foenum-graecum and Vigna subterranean possess bioactive compounds leading to cancer treatment. The important and mostly studied phytochemical compounds are Beta carotene, Alpha tocopherol, Alanine, Genestein, Caffeic acid, Tannin, Alpha carotene, Ascorbic acid, Limonene, Daidzein, Rutin and Niacin

Medicinal Plants,

Phytochemical Compound, Anticancer, Antitumor and Cancer Preventive Activities.

INTRODUCTION: Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. It has become a big threat to human beings globally. The high mortality rate among cancer patients is an indication of the limited efficiency of the current therapies including radiation therapy, chemotherapy, immunotherapy and surgery.

In recent years, focus on plant research by scientists and pharmacologists has increased all over the world and a large body of evidence has been accumulated to highlight the immense potential of medicinal plants used in various traditional systems of medicine ^{1, 2, 3}. Plants-derived compounds such as Beta carotene, Alpha-tocopherol, Alanine, fibre, Caffeic acid, Tannin, Kaempferol, Ascorbic acid, Limonene, Daidzein, Rutin, and niacin have played an important role in the development of several clinically useful anticancer agents ⁴.  Despite this encouraging preamble and the abundant literature describing the molecular mechanisms triggered by phytochemicals to inhibit cell growth and induce apoptosis in cancer cells, only a few of them entered clinical trials. So, the present study focuses on bioactive compounds found in the Fabaceae family which leads to cancer treatment. Further, the present study will explain the putative mechanism(s) of action of largely studied phytoresources from in vitro and in vivo studies, and the current status of their clinical applications in view of their realistic adoption as single chemotherapeutic agents or as chemosensitizers, in association with canonical and novel anticancer drugs.

 MATERIALS AND METHODS:

Data-mining of bioactive phytochemicals:

In the present study, the bioactive phytochemicals which are having potential of cancer treatment and cancer prevention were manually mining from publically available phytochemical databases (Dr. Duke’s phytochemistry and ethnobotanical database (www.ars-grin.gov/duke).

Collection and mining of literatures of bioactive compounds as therapeutic agents:

The literatures related to anticancer, antitumor cancer preventive activities of phytoresources were collected from publically available online sources.  The full texts of peer-reviewed scientific publications in a variety of journal were manually mining from the online sources such as Google scholar (http://scholar.google.co.in/) and pubmed (http://www.ncbi.nlm.nih.gov/pubmed). The said journal was selected to capture the greatest quantity of high-quality data in a cost, and time-effective manner. From each publication, details of the compounds tested, the assays performed and any target information for these assays were abstracted.

RESULTS AND DISCUSSION:

In Fabaceae family, there are 12 plant species were identified as lead for cancer drugs. They are such as Acacia nilotica, Arachis hypogaea, Cajanus cajan, Crotalaria juncea, Glycine max, Mimosa pudica, Pisum sativum, Psoralea esculenta, Tamarindus indica, Trifolium pratense, Trigonella foenum graecum and Vigna subterranea. These plant species possessed 106 bioactive compounds related to anticancer, antitumor anticarcinogenic and cancer preventive agents.  Among these phytochemical compounds, 23 phytochemical compounds were found to be possess anticancer activity, 49 phytochemical compounds possess antitumor activity, 15 phytochemical compounds possess Anticarcinogenic activity and 79 phytochemical compounds possess cancer preventive activity (Table 1).

TABLE 1: LIST OF PHYTOCHEMICAL COMPOUNDS PRESENT IN 12 PLANT SPECIES AND THEIR ANTICANCER, ANTITUMOR ANTICARCINOGENIC AND CANCER PREVENTIVE ACTIVITIES

1. 1. Acacia nilotica L:

Acacia nilotica is a large tree which is commonly called as Babul. In this plant, totally 19 cancer treatment bioactive compounds were identified in different parts (Table 3). Among them, 5 (26.32%) phytochemical compounds possessed anticancer activity, 13 (68.42%) phytochemical compounds possess antitumor activity, 10 (52.63%) phytochemical compound possess anticarcinogenic activity and 14 (73.68%) compounds possess cancer preventive activity.

Besides, 5 phytochemical compounds possess 3 combined activities such as anticancer, antitumor and cancer preventive activities or antitumor anticarcinogenic and cancer preventive activities. Similarly, 3 phytochemical compounds possess two activities such as cancer preventive and antitumor activities and Lignin have anticancer and antitumor activities (Table 2 and Fig. 1). The anticancer activity of this plant was studied by using various models by several authors. Gamma-sitosterol of A. nilotica exhibited potential anticancer activity through the growth inhibition, cell cycle arrest and the apoptosis on MCF-7 and A549 cells ⁵. The aerial parts of methanolic extract of Acacia nilotica have anticancer activity against Dalton’s ascetic lymphoma induced solid and ascetic tumor model ⁶.

TABLE 2: PHYTORESOURCES HAVING ANTICANCER, ANTITUMOR ANTICARCINOGENIC, AND CANCER PREVENTIVE ACTIVITIES

2. 2. Arachis hypogaea L:

Arachis hypogaea is commonly known as ground nut. It is an annual herbaceous plant. It has totally 37 phytochemical compounds in different parts such as leaf and seed (Table 3). Among them, 8 (21.62%) phytochemical compounds possess anticancer activity, 15 (40.54%) compounds possess antitumor activity, 3 (8.11%) compounds possess anticarcinogenic activity and 35 (94.59%) compounds possess cancer preventive activity. Besides, 5 compounds were identified to possess 3 activities such as anticancer, antitumor and cancer preventive activities in each of 5 compounds. Compounds like Chlorogenic acid and Ferulic acid possessed antitumor anticarcinogenic and cancer preventive activities (Table 2 and Fig. 1). Alike, some other 5 phytochemical compounds possess antitumor and cancer preventive activities. Resveratrol isolated from A. hypogaea exhibited anticancer activity against mouse xenograft models of human neuroblastoma and human colorectal cancer cells ⁷.

3. 3. Cajanus cajan L:

Cajanus cajan is commonly called Pigeon pea. It is a perennial shrub. There were 19 phytochemical compounds reported to have the ability of cancer treatment (Table 3). They found in leaf, fruit and seed of this plant. Among them, 89.47% (17) of compounds were reported that they possess cancer preventive activity. Four (21.05%) of them were reported as antitumor agents (Table 2 and Fig. 1). Apart from, Beta carotene is a single compound that possesses 3 activities such as anticancer, antitumor and cancer preventive activities. Root of Cajanus cajan plant arrested the cell cycle in the G2/m phase and induced apoptosis via a relative oxygen species (ROS) mediated mitochondria-dependent pathway ⁸.

4. 4. Crotalaria juncea L:

Crotalaria juncea is commonly called as Sun hemp. It is an herb. It has 5 cancer treatment compounds (Table 3). It includes 3 antitumour and 2 cancer preventive chemical compounds (Table 2 and Fig.1). Leaf extracts of C. juncea exhibited anticancer activity on human cervical cancer cell line. It might be due to the presence of the bioactive compounds ⁹.

5. Glycine max L:

Glycine max is commonly called Soyabean. It is a bushy herbaceous plant. Among the 12 plant species under study, G. max plant possesses 63 cancer treatment compounds (Table 3). Interestingly, 49 compounds were reported as cancer preventive agents. Similarly, 33, 16 and 4 compounds were used as antitumour, anticancer and anticarcinogenic drugs respectively. Some bioactive compounds found in this plant exhibited two or more activities (Table 2 and Fig.1). For example, Caffeic acid possesses 4 activities viz., anticancer, antitumor anticarcinogenic and cancer preventive activities. Bioactive compound aglycones isolated from ethylacetate extract of fermented G. max have antiproliferation activity against osteoblast cell line ¹⁰.

6. Mimosa pudica L:

Mimosa pudica is a pantropical weed which is commonly called as sensitive plant. It is a creeping annual or perennial herb. It contains eight phytochemical compounds with cancer treatment property. All these compounds possess cancer preventive activities. Among them, 3 were antitumour and 2 were anticancer agents (Table 2 & 3 and Fig.1). Flavanoids isolated from M. pudica has the high cytotoxic effect against MCF-7 human breast cancer cell line ¹¹. ITME (2011) reported that isolated 6 -glycosylflavone from Mimosa pudica possesses antitumor and antiproliferation activity on MCF-7 breast cancer cell line ¹². The pure compound L-Mimosine and hydroalcoholic extract of Mimosa pudica has antiproliferation activity on Lymphoma Daudi cells ¹³. The methanolic extract of M. pudica aerial part had cytotoxic activity ¹⁴.

7. Pisum sativum L:

Pisum sativum is commonly called as Pea. It is an herbaceous plant. Root, fruit and seed of P. sativum has 44 phytochemical compounds with cancer treatment properties (Table 3). Among them, 39 compounds, 17 compounds, 5 compounds, and 2 compounds were reported as cancer preventive, antitumour, anticancer and anticarcinogenic agents (Table 2 and Fig. 1). Methanolic extract of P. sativum showed anticancer activity against CaSki cells with IC₅₀ value of 14.8 ¹⁵.  Asperagenase enzyme isolated from P. sativum has a cytotoxic effect against L20B Tumor cell line ¹⁶.

8. Psoralea esculenta L:

Psoralea esculenta is commonly called Indian turnip. It is an herbaceous perennial plant. It has 8 phytochemical compounds with cancer treatment properties (Table 3). Beta carotene possesses anticancer activity and other 7 compounds of this plant possess cancer preventive activity. Although, this plant bears bioactive phytochemicals with anticancer, antitumor anticarcinogenic and cancer preventive activities compounds, there was no scientific reports available regarding its cancer treatment property.

9. 9. Tamarindus indica L:

Tamarindus indica is commonly called Tamarind. It is a leguminous tree. It contains 27 phytochemical compounds in different parts like leaf, fruit, flower, and seed (Table 3).   Among them, 4 (14.81%) phytochemical compounds possess anticancer activity, 7 (25.93%) phytochemical compounds possess antitumor activity, and 24 (88.89%) phytochemical compounds possess cancer preventive activity (Table 2 and Fig. 1). Limonene and tannin have anticancer, antitumor and cancer preventive activities, geraniol possesses antitumor and cancer preventive activities. PST001 isolated from the T. indica could suppress DLA and EAC cell growth and reduce the cell survival by reducing apoptosis of tumor cells ¹⁷. Polyphenolic compounds (2-hydroxy-dihydroxyaceophenone, (-) epicatechin, tannin, anthocyanidine and oligomeric proanthocyanidins) isolated from T. indica seeds have cancer related signal pathway blockage effect ¹⁸.

10. Trifolium pratense L:

Trifolium pratense is commonly called Red Clover or Cow Grass. It is a perennial sometimes biennial herb. It has 26 phytochemical compounds with cancer treatment properties and they were found in different parts like leaf, seed, flower, inflorescence, shoot, and stem (Table 3). Twenty five compounds of this plant possess cancer preventive activity and 10 possess antitumor activities (Table 2 and Fig. 1). Alpha tocopherol and beta carotene of this plant have anticancer, antitumor and cancer preventive activities. Chlorogenic acid possess antitumor anticarcinogenic and cancer preventive activities. Biochannin-a isolated from T. pratense inhibited carcinogen activity in hamster embryo cell culture ¹⁹.

ACA: Anticancer Activity; ATA: Antitumor Activity; ACAR A: Anticarcinogenic Activity; CPA: Cancer Preventive Activity

FIG. 1: PHYTORESOURCES HAVING ANTICANCER, ANTITUMOR ANTICARCINOGENIC, AND CANCER PREVENTIVE ACTIVITIES

 TABLE 3: PERCENT DISTRIBUTION OF CANCER TREATMENT PHYTOCHEMICAL COMPOUNDS IN 12 PLANT SPECIES OF FAMILY FABACEAE

11. Trigonella foenum-graecum L:

Trigonella foenum-graecum is commonly called Fenugreek. It is an annual herb. It contains 29 bioactive compounds with cancer treatment properties (Table 3).  Six compounds of this plant possess anticancer activity, 13 possess antitumor activity and 23 phytochemical compounds of it possess cancer preventive activities. Lignin possesses 3 activities such as antitumor anticarcinogenic and cancer preventive activities.  Fenugreek (T. foenum graecum) extracts exhibited cytotoxic effect on many type of cancers ²⁰.

12. Vigna subterranea L.:

Vigna subterranea commonly called Ground Bean. It is an annual, creeping lugume with glabrous, trifoliate leaves. It has 5 phytochemical compounds with anticancer activities (Table 3). V. subterranean showed preventive effect on lung cancer and liver cancer induced by morphine and sodium nitrite ²¹. Several animal studies of chemical induced carcinogenesis demonstrated that phytochemicals are able to inhibit cancer development (pre-initiation) and also able to cure cancer ^{22, 23, 24}. Due to the variety of their physiological roles in plant tissues in regulating enzymes involved in cell metabolism and in mechanisms of defence against foreign agents (radiations, viruses, parasites), phytochemicals have been associated to pleiotropic effects in animal cells. Phytochemicals attracted scientists’ interests since the demonstration that their biological targets in mammalian cells were the same involved in inflammatory processes and oncogenic transformation, such alterations of cell cycle control, apoptosis evasion, angiogenesis and metastases.

In addition, a large number of epidemiological studies suggested that a daily intake of phytochemicals can reduce the incidence of several types of cancers ²⁵.

CONCLUSION: In the present study, the anticancer activities of a group of phytochemicals representing good candidates for chemopreventive and chemotherapeutic applications have been reviewed. They have been selected from the available literatures. All compounds given in this paper are commonly found in the edible plants. They are cultivated by the farmers and some them naturally grow. All of them are available in the Indian vegetative environment. Well documented the presence of anticancer activities of these plants was supported by various experimental models, namely cell cultures and animal models of induced carcinogenicity. These molecules are largely cited in the current literatures and their activities are often associated with the term chemoprevention. The results of the present study may provide a foundation for designing new drug to ascertain the full chemopreventive and chemotherapeutic efficacy of phytochemicals.

ACKNOWLEDGEMENT: The authors thank the Management, the Principal and Head of the Department of Zoology, Nehru Memorial College, Puthanampatti, Tiruchirappalli district, Tamilnadu, India for providing necessary facilities to do this research work successfully. The third author thank to the University Grants Commission, New Delhi, for awarding Rajiv Gandhi National Fellowship (RGNF-JRF) for financial support.

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How to cite this article:

Velusamy B, Kaliyaperumal S and Raju A: Collection and Data-Mining of Bioactive Compounds with Cancer Treatment Properties in the Plants of Fabaceae Family. Int J Pharm Sci Res 2016; 7(5): 2065-73.doi: 10.13040/IJPSR.0975-8232.7(5).2065-73.

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