ANTICANCER AGENTS FROM SOME KNOWN PLANTS: A REVIEWinfokara.com/gallery/63-jan-3513.pdf · cancer cell lines (Wan Chick et al., 2010) revealed that purified sample gave a rational

ANTICANCER AGENTS FROM SOME KNOWN

PLANTS: A REVIEW

*UMARANI, B AND SARAVANAN, K

PG & RESEARCH DEPARTMENT OF ZOOLOGY,

NEHRU MEMORIAL COLLEGE (AUTONOMOUS),

(AFFILIATED TO BHARATHDASAN UNIVERSITY, TIRUCHIRAPPALLI)

PUTHANAMPATTI, TAMILNADU, INDIA.

*Corresponding author: [email protected]

ABSTRACT

Cancer is serious health problem which cause second leading cause of death worldwide. Even if

great advancements have been made in the treatment and control of cancer, a number of

undesired side effects will be occurred. Usage of plants and their derived products in cancer

treatments reduce adverse side effects and provide permanent cure. Currently, a few plants and

their secondary metabolites are being used to treat various types of cancer. However, an

innumerable product exists that have shown very promising anti-cancer properties in vitro and in

vivo conditions but have yet to be evaluated in humans. Further investigation is required to

determine the usefulness of these plant products in treating cancers in humans. This review

focused the therapeutic potential of traditional medicinal plants that can be used as drug

candidate in future to treat varies type of cancers.

Keywords: Medicinal plants; Phytochemicals; Anticancer activity.

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http://infokara.com/

mailto:[email protected]

INTRODUCTION

Medicinal plants are used in various fields of medicine, industry and agriculture application. In

the field of medicine, researcher focused herbs for treatment of cancer. Plants and their products

have been used since the early days of humankind and are still used throughout the world for

health promotion and treatment of disease. They form the basis of today’s modern medicine and

contribute largely to the commercial drug preparations manufactured today. About 25% of anti

cancer drugs prescribed globally are derived from medicinal plants. Due to the side effects of

drugs and chemicals in countries around the world, including developed countries are thinking

about changing pattern of drug by using of plants and their derived compounds. Some active

drug substances which are very important in the pharmaceutical industry are produce only

through natural plants (Niloufar karami et al., 2017).

Historically, medicinal plants drugs were used as tinctures, powders, poultices and teas followed

by formulations, and finally as pure compounds. Across the world cultures, knowledge about use

of herbs exists in the form of local folklore available within tribal families and societies cultures,

handed down from generation to generation. Further, they have been used for different ailments

and have provided valuable drugs such as analgesics (morphine), anti-tussives (codeine), anti-

hypertensives (reserpine), cardiotonics (digoxin), antineoplastics (vinblastine and taxol) and anti-

malarials (quinine and artemisinin) (Ramawat et al., 2007). Several authors studied anti-cancer

activity of large number plants using different models. The present review focuses and lists some

of the plants and their phytochemical compounds which possess anticancer activity.

PLANTS AND THEIR PHYTOCHEMICALS USED AS CANCER TREATMENT

In this review, we summarized natural phytochemicals and their anti-cancer effects (Table 1).

Capsicum annum L.( Solanaceae)

Capsicum annum is an annual herb. It is commonly called as Bell pepper or Chilli pepper. Many

authors reported that capsaicin isolated from capsicum annum has potent anticancer activity

against different types of cancer. It effectively work against both in vitro and in vivo against the

growth of prostate cancer cells inducing the apoptosis of both androgen receptor positive and

negative prostate cancer cell lines associated with an increase of antibodies p53, p21, and Bax

(Mori et al., 2006). Capsaicin isolated from capsicum annum has potent anti-tumor activity

against benzo (α) pyrene-induced lung tumorigenesis (Lee et al., 2011; Anandakumar et al.,

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2012). Capsaicin has a potent anti-cancer effect on human colorectal cancer (Lee et al., 2012;

Yang et al., 2013) by inducing autophagy, deregulation of B-catechin, and TCF dependent

signaling. Several authors studied anti-cancer activity of capsaicin on human breast cancer

against MCF-7, T47D, BT-474, SKBR-3 and MDA-MB231 cell lines where it inhibit cell

growth by causing mitochondrial dysfunction, increasing apoptosis and arresting cell cycle into

G2/M phase (Dou et al., 2011; Ip et al., 2011; Moon et al., 2012; Junior et al., 2013). Capsaicin

induced G0/G1 phase cell cycle arrest and apoptosis and ultimately arrest cell growth of PANC-1

cell line (Yang et al., 2013; Zhang et al., 2013; Datta et al., 2014). It also enhances apoptotic

effects by activating the calcium-CaMKII-Sp1 pathway on Hep3B cell lines (Moon et al., 2012)

and by decreasing cell viability, generated ROS, activated caspase-3, and autophagy on HepG2

cell line (Chen et al., 2016). Capsicum was also reported to be effective against gastric cancer

by inducing apoptosis and modulates MAPK signaling (Arnab et al., 2015; Park et al., 2014).

Cell cycle analysis indicated that exposure of KB cells to capsaicin resulted in cell cycle arrest at

G2/M phase (Arnab et al., 2015). From the review, it revealed that capsicum and its metabolites

capsaicin had potent anticancer activity against various types of cancer.

Lycopersicon esculentum L. ( Solanaceae)

Lycopersicon esculentum is an annual herb. It is commonly called Tomato. It is one of the

commonly used vegetables in the world. This plant is used in the treatment of several chronic

diseases such as cardiovascular diseases and certain types of cancer (Giovannucci, 1999). It is

reported that the fresh juice of tomato has been used as homemade folk medicine to cure oral

cancer and it is found to help prevent prostate cancer when it consumed cooked tomato

(Luckwill, 2003). Antiproliferative effects of lycopene isolated from tomato have been reported

in several cancer cell lines including prostate cancer cell lines (Hwang and Bowen, 2004; Tang et

al., 2005; Chalabi et al., 2006). Several in vivo studies supported the antiproliferative and

proapoptotic capabilities of lycopene or tomato components, such as in the in vivo transplantable

tumor models (Canene-Adams et al., 2007). A recent study has been employed with LNCaP

prostate cancer cell lines exposed to sera from volunteers who consumed tomato paste or purified

lycopene (Talvas et al., 2010). Expression array analysis of cells exposed to serum from patients

after red tomato consumption demonstrated several changes in pathways involved in cell

proliferation, apoptosis, and stress responses including cyclin D1, p53, Bax: Bcl-2, and IGFBP-3.

Another study on cytotoxicity effect of methanol extract of tomato leaves on MCF-7 breast

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cancer cell lines (Wan Chick et al., 2010) revealed that purified sample gave a rational effect

towards breast cancer cell line with 5.85 μg/ml IC50 value.

Solanum melongena L.( Solanaceae)

Solanum melongena is a half-hardy annual herb, native to the Indian Subcontinent. It is

commonly called as Brinjal. It is one of the widely used vegetables in India. Brinjal has high

antioxidant and phytochemical content which provides various therapeutic potential health

effects including cancer (Himanshu, 2017). Shabana et al., (2013) reported that the peels of S.

melongena fruits have a promising anticancer activity against hepatocellular carcinoma.

Solasonine, solasodine and solamargine isolated from brinjal induced significant antiproliferative

effect against liver cancer cells by arresting cell cycle at S-phase and inducing apoptosis (Fekry

et al., 2019). Further, they stated that glycoalkaloids derived from S. melongena is promising

antiproliferative agent with potential anticancer effects.

Solanum nigrum L. ( Solanaceae)

Solanum nigrum is an annual medicinal herb member of Family Solanaceae. It is commonly

called black night shade. S. nigrum is an extensively used medication where it is considered to be

anti-inflammatory, antioxidant, antiproliferative, antidiabetic, hepatoprotective and antipyretic

(Ramya et al., 2011). Both the crude extracts and isolated components of S. nigrum exhibited

antiproliferative effect on various cancer cell lines. Crude extract is prepared with dried berries

and from the whole plant. It has been observed that the treatment of high concentration of S.

nigrum crude extract on liver cancer cell lines (HepG2) activated proapoptotic factors like Bax

by activation of c-Jun N-terminal kinase (JNK). It further results in release of cytochrome c from

mitochondria that activates caspases and triggers apoptosis (Son et al., 2003). Chloroform extract

of whole plant of S.nigrum and alkaloid (Solanine) isolated from extract possess significant

anticancer potential against skin melanoma cancer (Romana et al., 2017). Crude extract of S.

nigrum have demonstrated antitumour effects in various types of cancer including human

melanoma and colorectal, endometrial, cervical and breast cancers (Huang et al., 2010; Wang et

al., 2010).

Solanum tuberosum L. ( Solanaceae)

Solanum tuberosum is included in the family Solanaceae and commonly called as Potato.

Extracts of this plant showed potent antiproliferative effect against different types of cancer cell

lines (Vizzotto et al., 2014; Ombra et al., 2015). Several laboratories studies also reported that

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the compounds, phenolic acids and anthocyanins isolated from S. tuberosum suppressed the

growth of cancer cell proliferation. (Galvano et al., 2004) caused apoptosis in cancer cells in a

dose dependent manner (Bontempo et al., 2013). Further scientific studies proved that the

phytochemicals of potato showed potent healing activity and it would be significant in lowering

the risk of cancer (Sahir et al., 2018). Therefore, the phenolic compounds from potato are

considered natural products which beneficial to reduce the risk of cancer.

Withania somnifera L. ( Solanaceae)

Withania sominifera is a short shrub. It is commonly called as Aswagandha. Ethanolic extracts of

W. somnifera induced apoptosis against breast cancer cell line and also arrested G2/M cell cycle

(Agarwal et al., 2006). Fruit extract of W. somnifera showed antiproliferative activity against

breast, lung and colon cancer cell lines (Maliyakkal et al., 2013). Further, plant tissue of W.

somnifera have varieties of physiological roles including regulation of metabolic enzymes and

protect our body against foreign substances like radiations, viruses and some parasitic organisms

(Sporn and Surh, 2002; Surh, 2003). An in vivo study proved that phytochemical withaferin-A

from W. somnifera shown significant anticancer activity (Singh et al., 2010).

Curcuma longa (Zingiberaceae)

Curcuma longa is an herbaceous perennial plant belonging to the family Zingiberaceae which

native to tropical South Asia. It is commonly known as Turmeric. It is used as spice as and it is

extensively used in medicinal system such as Siddha, Ayurveda, and Unani. The extract of C.

longa exhibited anticancer activities against different cancer cell lines (Sushma Kainsa et al.,

2012). Curcumin from C. longa act as a good anticancer agent due to its potent antiproliferative

activity and apoptotic activity in various cancer cell lines (Collett et al., 2001; Rathaur et al.,

2012).

Zingiber officinale (Zingiberaceae)

Zingiber officinale is an herbaceous and perennial plant native to India. It is commonly known as

zinger. It included in the family Zingiberaceae. The rhizome of this plant is widely used as a

common condiment for preparation of various foods and beverages. In India Ginger has

traditionally used for various medicinal purposes like headaches, nausea, rheumatism, and colds

(Rajesh et al., 2012). Extract of Zingiber officinale leaves exhibited great potent of anticancer

effect against MCF-7, MDA-MB-231 and HepG-2 cells. It reduced cell viability and induced

apoptosis in dose dependent manner (Park et al., 2014). The methanolic extract of Zingiber

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officinale rhizome (ZOME) exhibited anticancer activity against cervical cancer cells (HeLa) and

breast cancer (MDA-MB-231) cells (Ansari et al., 2016).

Malus domestica (Rosaceae)

Malus domestica is deciduous tree. It is well known by the world for its delicious and nutritious

fruits (Mc Cann et al., 2007). Researchers have advocated that apples are rich sources of

antioxidant compounds that may reduce the risk of cancers (Gerhauser, 2008; Nour et al., 2010).

Essential oil of M. domestica leaves exhibited great extent of anticancer activity (98.2%) on C-6

(glioma cells) cell line at concentration of 2000µg/ml (Salazar et al., 2011). Earlier a study

reported that triterpenoids isolated from apple peels showed potent antiproliferative and

anticancer activity (Xiangjiu and Rui, 2007).

Prunus armeniaca L. (Rosaceae)

Prunus armeniaca is a small tree commonly called apricot. In England, apricot oil is used against

tumor growth, inflammations and ulcers even from the seventeenth century (Chang et al., 2006).

Cyanogenic glycosides (mainly amygdalin) present in the seeds of these plants are used as a

medicament for the treatment of cancer (Yang et al., 2006). The extracts of P. armeniaca

showed inhibitory activity against different cancer cell lines like breast cancer (MCF-7), colon

cancer (HCT-116), and hepatocellular (Hep-G2) carcinoma cell lines in a dose-dependent

manner with different sensitivity (Gomaa, 2013).

Prunus domestica L. (Rosaceae)

Prunus domestica is a flowering plant included in the family Rosaceae. The ethanol extract of P.

domestica exhibited antiproliferative and apoptotic activity in human colon carcinoma cells

(Akcicek et al., 2005). Chlorogenic acid isolated from the ethyl acetate fraction of P. domestica

fruit showed great extend of antioxidant as well as anti-proliferative activity (Joshi et al., 2005).

Pyrus communis L. (Rosaceae)

It is commonly known as European pear. Consumption of this fruit on regular basis prevents

bladder, lungs and esophageal cancers (Kaur and Arya, 2012). Urosolic acid from pear inhibited

cancer proliferation and preventing cancer (Linseisen et al., 2007; Buchner et al., 2009).

Rosa canina L. (Rosaceae)

It is commonly called as dog-rose. The different fractions of Rosa canina showed inhibitory

effect on human tumor cell proliferation by inducing apoptosis (Willingham, 1999). The extract

of R. canina containing quercetin effectively work against cancer cell proliferation of HeLa

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(Cervical cancer), MCF7 (Breast cancer) and HT-29 (Colon cancer) cell lines (Tumbas et al.,

2012). Polyphenols and vitamin C from extraction of rosehips exhibited antiproliferative effect

against different cancer cell lines (Jimenez et al., 2016). Ascorbic acid and P-coumaric acid from

fraction of R. canina showed cytotoxic effect on A549 lung cancer cell line (Kagan et al., 2019).

Rubus fruticosus (Rosaceae)

Rubus fruticosus L is the name of Blackberry. Blackberry extract inhibited the cell proliferation

of cancer cell by inducing apoptosis in human leukemia cell line (HL-60) (Weber and Liu,

2002). Phytochemicals from black berry extract preventing oesophageal cancer in rodents

(Stoner, 2006). Anthocyanin from Rubus fruticosus protect against various kinds of cancers

(Archivio and Masella, 2007).

Hibiscus sabdariffa L (Malvaceae)

Hibiscus sabdariffa is an annual erect, bushy, herbaceous shrub which native from India. It is

commonly known as sorrel. The methanol extract of H. sabdariffa showed effective anticancer

activity on hepatocarcinoma cell line (Umamaheswari and Nivedita, 2007). The aqueous extract

of H. sabdariffa exhibited antibreast cancer activity (Shahnaz Khaghani et al., 2011). The leaf

extract of H sabdariffa showed anticancer effect against lung cancer cell line (Worawattananutai

et al., 2014) prostate cancer cell line (Chiu et al., 2015).

Abelmoschus esculentus (Malvaceae)

It is an annual or perennial herb. It is commonly known as ladies finger. The phytocompounds

carotene, vitamin B and C, and amino acids present in the Abelmoscus esculentus inhibited the

growth of cancer cells (Pandey and Madhuri, 2011). The flower extract of A. esculentus showed

significant anticancer activity against HepG2 cell line (Solomon et al., 2016). The rich amount of

flavonoid present in the seed extract of A. esculentus which showed highest toxic effect on breast

cancer, hepatocellular carcinoma and cervical carcinoma (Watcharaphong et al., 2019).

Thespesia populnea (Malvaceae)

Thespesia populnea is a tree and it has a pantropical distribution. It is commonly called tulip tree.

The ethanolic extract of bark of T. populnea showed potent anticancer effect in DMBA induced

breast cancer rat (Sasikumar et al., 2010). The acetone extract of T. populnea exhibited

anticancerous effect on Hep2 cell lines (Jeyaseeli et al., 2016).

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Mentha spicata (Lamiaceae)

Mentha spicata is a herbaceious perennial plant. Methanol and chloroform extract of M. spicata

exhibited great extent of cytotoxic effect (80%) against HeLa, Hep-2 and PC-3 cancer cell lines

(Arumugam et al., 2010; Rahimifard et al., 2010). Aqueous extract of M. spicata leaves showed

anticancer effect on mouse fibrosarcoma cells (wehi-164) as well as human monocytic leukemia

(U937) cells (Hajighasemi et al., 2011).

Plectranthus amboinicus (Lamiaceae)

Plectranthus amboinicus is a large succulent herb. It is commonly called Indian borage. The

extract of P. amboinicus has potent cytotoxic activity against HeLa cell line (Rosidah et al.,

2014). The combination of ethyl acetate extract of P. amboinicus with doxorubicin could

increase the cell cycle arrest, inducing apoptotic and decrease cyclin D1 and cox-2 expressions

(Hasibuan et al., 2015). Ethanolic extract of P. amboinicus showed significant anticancer activity

against MCF-7 cancer cell line (Bowya et al., 2016).

Tectona grandis (Lamiaceae)

Tectona grandis is a large, deciduous tree. It is commonly called teak. T. grandis extracts

demonstrated highly significant activity against cancerous tumors in rats (Bhangale et al., 2010).

The ethyl acetate extract of T. grandis showed potent anti-breast cancer activity against MCF-7

cells (Arul Priya et al., 2019).

Ocimum sanctum (Lamiaceae)

Ocimum sanctum is an erect, much branched medicinal herb. It is commonly called holy basil.

Several authors reported the anticancer activity of O. sanctum on various cell lines. Sridevi et al

(2016) reported that extract of O. sanctum showed cytotoxic effect on cancer cells by decreasing

cell multiplication, alternation in mitochondrial membrane potential, increasing intracellular

ROS and apoptosis in NC1-H460 cell line. O. sanctum exhibited anticancer activity on

fibrosarcoma cells (Kartikeyan et al., 1999). Methanolic extract of O. sanctum exhibited cancer

preventive activities in the course of reduction of overload amount of nitric oxide. Ethanolic

extract of basil leaves found to produce significance reduction in tumor incidence (Papillomas)

in the skin of albino mice (Kim et al., 1998). Eugenol isolated from holy basil showed great

extent of anticancer effect (Prashar et al., 1994). Phytochemical compounds Eugenol, Linoleic

acid, β-sitosterol from O. sanctum prevented skin, liver, oral and lung cancers by increasing the

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antioxidant activity, inducing apoptosis, altering the gene expression and inhibiting metastasis

(Baliga et al., 2013).

Acacia nilotica L (Fabaceaea)

Acacia nilotica is a large tree which is commonly called as babul. The anticancer activity of this

plant was studied by several authors using various models. The aerial parts of methanolic extract

of A. nilotica have anticancer activity against Dalton’s ascetic lymphoma induced solid and

ascetic tumor model (Sakthivel et al., 2012). 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 (Sundaraj et al., 2012).

Pisum sativum (Fabaceaea)

P. sativum also known as green pea and included in the family Fabaceae. It has long been an

important part of a healthy diet due to its contents (protein, starch, fiber, trace minerals, and

phytochemicals). Also, the plant has been shown to possess many biological activities including

anticancer properties. The extract of P. sativum has pharmacologically active and potent

anticancer effect (Clemente et al., 2005). The ethanol extracts of Pisum sativum showed great

anticancer activity against MCF-7 cells (Arul Priya et al., 2018).

CONCLUSION

Medicinal plants are rich sources of herbal properties contributing in the discovery of new drugs

towards various disorders, diseases including cancer without any toxic effects on the individuals

treated. Treatment of cancer by use of natural products and traditional medicine by applying the

concepts of Ayurveda is attaining a great significance scope of cancer research. In the present

review we presented the used of some common plants and their compound in cancer treatment. It

will be helpful to design a new safe drug for the treatment of cancer.

ACKNOWLEDGEMENT

The authors thank the Management, the Principal and Head of the Department of Zoology,

Nehru Memorial College, Puthanampatti, Tirchy for providing necessary facilities to do this

research work successfully. The first author thank to the University Grants Commission, New

Delhi, for awarding Rajiv Gandhi National Fellowship (RGNF-SRF) and financial support.

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Table 1: Medicinal plants and their compounds used in the treatment of cancer.

S.No Plant Name Family Common name Compounds

1. Capsicum annum Solanaceae Chillies Capsaicin

2. Lycopersicon esculentum

L.

Solanaceae Tomato Lycopene

3. Solanum melongena L. Solanancea Brinjal/egg plant Solasonine,

Solasodine,

Solamargine,

Glycoalkaloids

4. Solanum nigrum L. Solananceae Blackberry Solanine

5. Solanum tuberosum L. Solananceae Potato Phenolic acids,

Anthocyanins

6. Withania somnifera L. Solanaceae Ashwagandha Withaferin-A

7. Curcuma longa Zingiberacea

e

Turmeric Curcumin

8. Zingiber officinale Zingiberacea

e

Zinger -

9. Malus domestica Rosaceae Apple Triterpenoids

10. Prunus armeniaca L. Rosaceae Armenian plum Cyanogenic glycosides

11. Prunus domestica L. Rosaceae Common plum Chlorogenic acid

12. Pyrus communis L. Rosaceae European pear Urosolic acid

13. Rosa canina L. Rosaceae Dog rose Quercetin,

Polyphenols, Vitamin

C, Ascorbic acid, P-

coumaric acid

14. Rubus fruticosus Rosaceae Black berry Anthocyanin

15. Hibiscus sabdariffa L Malvaceae Carcade, roselle ---

16. Abelmoschus esculentus Malvaceae Okra Carotene, Vitamin B

and c and Amino acids,

Flavonoid.

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17. Thespesia populnea Malvaceae Rosewood ---

18. Mentha spicata Lamiaceae Mint ---

19. Plectranthus amboinicus Lamiaceae Mexican mint ---

20. Tectona grandis Lamiaceae Teak ---

21. Ocimum sanctum Lamiaceae Holy basil Eugenol, Linoleic acid,

β-sitosterol

22. Acacia nilotica Fabaceaea Babul Gamma-sitosterol

23. Pisum sativum Fabaceaea Green pea ---

1.

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