Natural Bioactive Compound with Anticancer Potential
Keywords:
Herbs, Cancer, Flavonides, AnthraquinonesAbstract
Natural product drugs play a dominant role in pharmaceutical care. Nature is an attractive source of new therapeutic candidate compounds as a tremendous chemical diversity is found in millions of species of plants, animals, marine organisms and microorganisms. Several plant-derived compounds are currently successfully employed in cancer treatment. There are many classes of plantderived cytotoxic natural products studied for further improvement and development of drug. Interest has revived recently in the investigation of medicinal plants to identify novel active phytochemicals that might lead to drug development. New anticancer drugs derived from research on plant antitumor agents will be continuously discovered. The activities of flavonoids and the synergistic action shown by them with other drugs make them ideal in alternative cancer therapies. Induction of apoptosis is commonly reported among emodin and aloe-emodin, which involve disruption of mitochondria membrane potential, cytochrome c release, and activation of caspase 3. Emodin and aloe-emodin were also able to induce cell-cycle arrest, involving an increase in p53 expression level and accompanied by upregulation of p21.
References
Farnsworth NR, Akerele O, Bingel AS, Soejarto
DD, Guo Z.Medicinal plant in therapy. Bull World
Health Organ 1985, 63:965-981.
Cragg GM, Newman DJ, Snader KM. Natural
Products in Drug Discovery and Development. J
Nat Prod 1997, 60:52-60.
Balandrin MF, Kinghorn AD, Farnsworth NR: In
Human Medicinal Agents from Plants. Edited by
Kinghorn AD, Balandrin MF. North Carolina,
USA: Oxford University Press USA; 1993:2-12.
[American Chemical Society Symposium Series.]
Farnsworth NR. The role of ethnopharmacology in
drug development. Ciba Found Symp 1990,
:211.
Cragg GM, Newman DJ. Discovery and
development of antineoplastic agents from natural
sources. Cancer Invest 1999, 17:153-163.
http://www.all4naturalhealth.com/herbs-forcancer.html
Schwartsmann G. Marine organisms and other
novel natural sources of new anticancer agents.
Ann Oncol 2000, 11:235-243.
Schwartsmann G, Rocha AB, Berlinck R, Jimeno
J. Marine organisms as a source of new anticancer
drugs. Lancet Oncol 2001, 2:221-225.
Wang HK, Lee KH. Plant-derived anticancer
agents and their analogs currently in clinical use or
in clinical trials . Bot Bull Acad Sinica 1997;
:225.
Lee KH. Biopharma Quart 1998; 3:12.
Barnett CJ, Cullinan GJ, Gerzon K, Hoying RC,
Jones WE, Newlon WM, Poore GA, Robison RL,
Sweeney MJ, Todd GC, Dyke RW, Nelson RL.
Structure-activity relationships of dimeric
Catharanthus alkaloids 1. Deacetyl vinblastine
amide (vindesine) sulfate.J Med Chem 1978;
:88.
Barnett CJ, Cullinan GJ, Gerzon K, Hoying RC,
Jones WE, Newlon WM, Poore GA, Robison RL,
Sweeney MJ, Todd GC, Dyke RW, Nelson RL.
Structure-activity relationships of dimeric
Catharanthus alkaloids 1. Deacetyl vinblastine
amide (vindesine) sulfate. J Med Chem 1978;
:88.
Cragg G, Suffness M. Metabolism of plant-derived
anti-cancer agents.Pharmac Ther 1988; 37:425.
Wall ME, Wani MC, Cook CE, Palmer KH,
McPhail AT, Sim GA. Noval antitumor agents
from higher plants .J Am Chem Soc 1966;
:3808.
Wani MC, Nicholas AW, Wall ME. Plant
antitumor agents 23. Synthesis and antileukemic
activity of camptothecin analogs. J Med Chem
; 29:2358.
Johnson PK, McCabe FL, Faucette LF, Hertzberg
RP, Kingsbury WD, Boehm JC, Caranfa MJ,
Holden KG. Proc Amer Assoc Cancer Res 1989;
:623.
Camptothecins: New Anticancer Agents. Potmesil
M, Pinedo M, editors. Boca Raton, FL: CRC;
p 113.
Fukuoka M, Negoro S, Niitani H, Taguchi T. Proc
Amer Soc Clin Oncol 1990; 9:874.
Kawato Y, Aonuma M, Hirota Y, Kuga H, Sato K.
Intracellular Roles of SN-38, a Metabolite of the
Camptothecin Derivative CPT-11, in the
Antitumor Effect of CPT-11.Cancer Res
;51:4187.
Camptothecins: New Anticancer Agents. Potmesil
M, Pinedo M, editors. Boca Raton, FL: CRC;
p 67.
Keller-Juslen C, Kuhn M, von Wartburg A,
Stahelin H. Mitosis-inhibiting natural products. 24.
Synthesis and antimitotic activity of glycosidic
lignan derivatives related to podophyllotoxin. J
Med Chem 1971; 14:936.
O'Dwyerm PJ, Alonso MT, Leyland-Jones B,
Marsoni S. Teniposide: A review of 12 years of
experience. Cancer Treat Rep 1984; 68:1455.
VePesid product information overview. Bristol
Lab;1983.
Etoposide (VP-16) current status and new
developments. Issell BF, Muggia FM, Carter SK,
editors. Orlando, FL: Academic; 1984.
Zhou XM, Lee KJH, Cheng J, Wu SS, Chen HX,
Guo X, Cheng YC, Lee KH. Antitumor agents.
New gamma-lactone ring-modified arylamino
etoposide analogs as inhibitors of human DNA
topoisomerase II. J Med Chem 1994; 37:287.
Bastow KF, Wang HK, Cheng YC, Lee KH.
Antitumor agents--CLXXIII. Synthesis and
evaluation of camptothecin-4 beta-amino-4'-Odemethyl epipodophyllotoxin conjugates as
inhibitors of mammalian DNA topoisomerases and
as cytotoxic agents. Bioorg Med Chem 1997;
:1481.
Kashiwada Y, Nonaka G, Nishioka I, Lee KJ, Bori
I, Fukushima Y, Bastow KF, Lee KH.
Tannins as Potent Inhibitors of DNA Topoisomerase II
In Vitro. J Pharm Sci 1993; 82:487.
Kashiwada Y, Nonaka G, Nishioka I, Chang JJ,
Lee KH. Antitumor Agents, 129. Tannins and
Related Compounds as Selective Cytotoxic
Agents. J Natl Prod 1992; 55:1033.
Bastow KF, Bori ID, Fukushima Y, Kashiwada Y,
Tanaka T, Nonaka G, Nishioka I, Lee KH.
Inhibition of DNA Topoisomerases by Sanguiin H-
, a Cytotoxic Dimeric Ellagitannin from
Sanguisorba officinalis .Planta Med 1993; 59:240.
Chen CH, Yang LM, Lee TTY, Shen YC, Zhang
DC, Pan DJ, McPhail AT, McPhail DR, Liu SY, Li
DH, Cheng YC, Lee KH. Antitumor agents--CLI.
Bis(helenalinyl)glutarate and bis(isoalantodiolB)glutarate, potent inhibitors of human DNA
topoisomerase II. Bioorg Med Chem 1994; 2:137.
Kashiwada Y, Bastow KF, Lee KH. Novel lignan
derivatives as selective inhibitors of DNA
topoisomerase II . Bioorg Med Chem Lett 1995;
:905.
Lee KH, Imakura T, Sumida Y, Wu RY, Hall IH,
Huang HC. Antitumor agents 33. Isolation and
structural elucidation of bruceoside -A and -B,
novel antileukemic quassinoid glycosides, and
brucein -D and -E from Brucea javanica . J Org
Chem 1979; 44:2180.
Fukamiya N, Okano M, Miyamoto M, Tagahara K,
Lee KH. Antitumor Agents, 127. Bruceoside C, a
New Cytotoxic Quassinoid Glucoside, and Related
Compounds from Brucea javanica. J Natl Prod
; 55:468.
Onishi S, Fukamiya N, Okano M, Tagahara K, Lee
KH. Bruceosides D, E, and F, three new cytotoxic
quassinoid glucosides from Brucea javanica. J Natl
Prod 1995; 58:1032.
Kupcahn SM, Britton RW, Lacadie JA, Ziegler
MF, Sigel CW. The isolation and structural
elucidation of bruceantin and bruceantinol, new
potent antileukemic quassinoids from Brucea
antidysenterica. J Org Chem 1975; 40:648.
Walle T, Otake Y, Brubaker JA, Walle UK,
Halushka PV. 2001. Disposition and metabolism of
the flavonoid chrysin in normal volunteers. Br J
Clin Pharmacol 51: 143–146.
Mukhtar H, Das M, Khan WA, Bik DP. 1988.
Exceptional activity of tannic acid among naturally
occurring plant phenols in protecting against 7,12-
dimethybenz(a)anthraxcene-, benzo(a)pyrene-, 3-
methylcholanthrene-, and N-methyl-Nnitrosoureainduced skin tumorigenesis in mice. Cancer Res
: 2361–2365.
Kuntz S, Wenzel U, Daniel H. 1999. Comparative
analysis of the effects of flavonoids on
proliferation, cytotoxicity, and apoptosis in human
colon cancer cell lines. Eur J Nutr 38: 133–142.
Knowles LM, Zigrossi DA, Tauber RA, Hightower
C, Milner JA. 2000. Flavonoids suppress
androgen-dependent human prostatic tumor
proliferation. Nutr Cancer 38: 116–122.
Polkowski K, Mazurek AP. 2000. Biological
properties of genistein. A review of in vitro and in
vivo data. Acta Pol Pharm Drug Res 57: 135–155.
Valcic S, Timmermann BN, Alberts DS et al.
Inhibitory effect of six green tea catechins
and caffeine on the growth of four selected human
tumor cell lines. Anticancer Drugs 7: 461–468.
Scambia G, Raneletti FO, Panici PB et al. 1990.
Synergistic antiproliferative activity of quercetin
and cisplatin on ovarian cancer cell growth.
Anticancer Drugs 1: 45–48.
Scambia G, Raneletti FO, Panici PB et al. 1992.
Inhibitory effect of quercetin on primary ovarian
and endometrial cancers and synergistic activity
with cis diamminedichloroplatinum (II). Gynecol
Oncol 45: 13–19.
Scambia G, Ranelletti FO, Panici PB et al. 1994.
Quercetin potentiates the effect of adriamycin in a
multidrug-resistant MCF-7 human breast-cancer
cell line: P-glycoprotein as a possible target.
Cancer Chemotherapy Pharmacol 34: 459–464.
Versantvoort CHM, Schuurhuis GJ, Pinedo HM et
al. 1993. Genistein modulates the decreased drug
accumulation in non-P-glycoprotein mediated
multidrug resistant tumour cells. Br J Cancer 68:
–946.
Zhang L, Chang CJ, Bacus SS, Hung MC.
Suppressed transformation and induced
differentiation of HER- 2/neu-overexpressing
breast cancer cells by emodin. Cancer Res 1995;
:3890.
Lee HZ, Hsu SL, Liu MC, Wu CH. Effects and
mechanisms of aloe-emodin on cell death in
human lung squamous cell carcinoma. Eur J
Pharmacol 2001; 431:287–295.
Yeh FT, Wu CH, Lee HZ. Int J Cancer 2003;
:26–33.
Kuo PL, Lin TC, Lin CC. The antiproliferative
activity of aloe-emodin is through p53-dependent
and p21- dependent apoptotic pathway in human
hepatoma cell lines. Life Sci 2002; 71:1879–1892.
Chen HC, Hsieh WT, Chang WC, Chung JG.
Aloe-emodin induced in vitro G2/M arrest of cell
cycle in human promyelocytic leukemia HL-60
cells. Food Chem Toxicol 2004; 42:1251–1257.
Pecere T, GazzolaMV, Mucignat C, Parolin
C,Vecchia FD, Cavaggioni A, Basso G, Diaspro A,
Salvato B, Carli M, Palu G. Aloe-emodin is a new
type of anticancer agent with selective activity
against neuroectodermal tumors. Cancer Res 2000;
:2800–2804.
Pecere T, Sarinella F, Salata C, Gatto B, Bet A,
Dalla Vecchia F, Diaspro A, Carli M, Palumbo M,
Palu G.Involvement of p53 in specific antineuroectodermal tumor activity of aloe-emodin. Int
J Cancer 2003; 106:836–847.
Kuo PL, Hsu YL, Ng LT, Lin CC. Rhein inhibits
the growth and induces the apoptosis of Hep G2
cells. Planta Med 2004; 70:12–16.
Acevedo-Duncan M, Russell C, Patel S, Patel R.
Aloe-emodin modulates PKC isozymes, inhibits
proliferation, and induces apoptosis in U-373MG
glioma cells. Int Immunopharmacol 2004; 4:1775–
Kamei H, Koide T, Kojima T, HashimotoY,
Hasegawa M. Inhibition of cell growth in culture
by quinones. Cancer Biother Radiopharm 1998;
:185.
Sanjeev Banerjee, Zhiwei Wang, Mussop
Mohammad, Fazlul H. Sarkar, and Ramzi M.
Mohammad. Efficacy of Selected Natural Products
as Therapeutic Agents against Cancer. J. Nat.
Prod. 2008, 71, 492–496
