|Year : 2019 | Volume
| Issue : 1 | Page : 1-7
Natural phenolics: a source of anticancer agents
Mohamed Amin El-Ansari, Lamyaa Fawzy Ibrahim, Mohamed Sharaf
Phytochemistry and Plant Systematics Department, National Research Centre, Dokki, Cairo, Egypt
|Date of Submission||30-Oct-2018|
|Date of Acceptance||06-Dec-2018|
|Date of Web Publication||26-Mar-2019|
Lamyaa Fawzy Ibrahim
Phytochemistry and Plant Systematics Department, National Research Centre, Dokki-12311, Cairo
Source of Support: None, Conflict of Interest: None
Cancer is a worldwide scourge, which affects people of all ages, and is rapidly becoming a global pandemic. It is one of the main leading causes of death especially in developing countries. Mankind has been trying hard to find better and cheaper treatments with fewer side effects to reduce the incidence of the disease and its consequent mortality. Natural phenolics play an important role in cancer prevention and treatment. Phenolics from medicinal plants are responsible for their chemopreventive properties and also contribute to their activity as apoptosis inducers. For many years, phenolic compounds have been intensely studied, in vitro and in vivo, for their antitumor effects. In recent years, the use of these compounds has increased considerably. In this regard, this article provides an overview of some natural phenolic compounds with approved anticancer activities.
Keywords: anticancer activity, medicinal plants, natural phenolics
|How to cite this article:|
El-Ansari MA, Ibrahim LF, Sharaf M. Natural phenolics: a source of anticancer agents. Egypt Pharmaceut J 2019;18:1-7
Phenolic compounds comprise a broad class of natural products formed mainly by plants, as well as microorganisms and marine organisms. Nowadays the interest in these compounds has increased mainly due to their diverse chemical structure and various biological activities, which is valuable in the prevention of some chronic or degenerative diseases. Phenolic compounds are widely dispersed throughout the plant kingdom representing about 9000 different phenolic structures. As secondary metabolites they also display defensive growth and development effects. They have at least one aromatic ring with one or more hydroxyl groups attached, being able to range from low molecular weight molecules to high molecular weight complex ones. Phenolic compounds generally appear as esters and glycosides rather than as free compounds due to the conferred stability of these molecules. This family of compounds is one of the most widely studied families and had been published in numerous reports due to their beneficial effects in various aspects of human health and well-being ,,.
Since ancient times, plants have been used as remedies to treat different types of illnesses showing satisfying results. Today, more than 60% of anticancer drugs originate either from natural compounds or are derived from them, making these bioactive molecules increasingly promising for drug companies, even as prototypes of final formulations for anticancer drugs ,.
The antioxidant activity of the phenolic compounds depends on their structure, in particular the number, positions of the hydroxyl groups, and the nature of substitutions on the aromatic rings. [Table 1] outlines the most important groups of plant phenolics .
| Plant phenolics with anticancer activity|| |
Cancer is a growing public crisis. The estimated worldwide new incidences are about six million cases per year. It is the second major cause of death after cardiovascular diseases. A large number of plants have been tested for their anticancer activities, and plenty of compounds have survived to be potential leads.
The therapeutic effect of some isolated natural phenolics on malignant tumors are tabulated in [Table 2]. The name of the natural phenolic compound, the natural source (representative species and family) and the references are provided. Structures of some selected phenolic compounds are shown in [Figure 1].
| Conclusion|| |
Plants have been a prime source of highly effective conventional drugs for the treatment of many types of cancer. In many instances, the actual compounds isolated from the plants may not serve as a drug, but lead to the development of potential novel agents. With the development of new technologies, some of the natural tested compounds which have failed in earlier clinical studies are now stimulating renewed interest. The ability to attach agents to carrier molecules directed to specific tumors holds promising results for the effective targeting of highly cytotoxic natural products against tumors, while avoiding their toxic side effects on normal healthy tissues. With the urgent need for the detection of new proteins having significant regulatory effects on tumor cell cycle progression, and their conversion into valuable natural targets, molecules isolated from plants and other natural organisms are proving to be an important source of novel inhibitors of the action of these key proteins and have the potential for development into selective anticancer agents.
The authors thank the National Research Centre (NRC) for the facilities provided.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Fraga GC. Plant phenolics and human health: biochemistry, nutrition and pharmacology. Hoboken, NJ: John Wiley & Sons; 2010.
Boudet A. Evolution and current status of research in phenolic compounds. Phytochemistry 2007; 68:2722–2735.
Lule SU, Xia W. Food phenolics, pros and cons: a review. Food Rev Int 2005; 21:367–388.
Rocha AB, Lopes RM, Schwartsman G. Natural products in anticancer therapy. Curr Opin Pharmacol 2001; 1:364–369.
Gordaliza M. Natural products as leads to anticancer drugs. Clin Transl Oncol 2007; 9:767–776.
Harborne JB. Plant phenolics. In: Bell EA, Charlrwood BV, editors. ‘Encyclopedia of plant physiology’, vol. 8, Secondary plant products. Berlin New York: Springer-Verlag 1980. pp. 329–395.
Wei Y, Zhao X, Kariya Y, Fukata H, Teshigawara K, Uchida A. Induction of apoptosis by quercetin: involvement of heat shock protein. Cancer Res 1994; 54:4952–4957.
Tan W, Lin L, Li M, Zhang Y, Tong Y, Xiao D, Ding J. Quercetin, a dietary-derived flavonoid, possesses antiangiogenic potential. Eur J Pharmacol 2003; 459:255–262.
Nair H, Rao KVK, Aalinkeel R, Mahajan S, Chawda R, Schwartz SA. Inhibition of prostate cancer cell colony formation by the flavonoid quercetin correlates with modulation of specific regulatory genes. Clin Diagn Lab Immunol 2004; 11:63–69.
Mylonis I, Lakka A, Tsakalof A, Simos G. The dietary flavonoid kaempferol effectively inhibits HIF-1 activity and hepatoma cancer cell viability under hypoxic conditions. Biochem Biophys Res Commun 2010; 398:74–78.
Zhang Y, Chen AY, Li M, Chen C, Yao Q. Ginkgo biloba
extract kaempferol inhibits cell proliferation and induces apoptosis in pancreatic cancer cells. J Surg Res 2008; 148:17–23.
Yoshida T, Konishi M, Horinaka M, Yasuda T, Goda AE, Taniguchi H et al.
Kaempferol sensitizes colon cancer cells to TRAIL-induced apoptosis. Biochem Biophys Res Commun 2008; 375:129–133.
Lu Y, Jiang F, Jiang H, Wu K, Zheng X, Cai Y et al.
Gallic acid suppresses cell viability, proliferation, invasion and angiogenesis in human glioma cells. Eur J Pharmacol 2010; 641:102–107.
Ji B, Hsu W, Yang J, Hsia T, Lu C, Chiang J et al.
Gallic acid induces apoptosis via caspase-3 and mitochondrion-dependent pathways in vitro and suppresses lung xenograft tumor growth in vivo. J Agric Food Chem 2009; 57:7596–7604.
Umesalma S, Sudhandiran G. Ellagic acid prevents rat colon carcinogenesis induced by 1, 2 dimethyl hydrazine through inhibition of AKT-phosphoinositide-3 kinase pathway. Eur J Pharmacol 2011; 660:249–258.
Alias LM, Manoharan S, Vellaichammy L, Balakrishnan S, Ramachandran CR. Protective effect of ferulic acid on 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis in Swiss albino mice. Exp Toxicol Pathol 2009; 61:205–2014.
Baskaran N, Manoharan S, Balakrishnan S, Pugalendhi P. Chemopreventive potential of ferulic acid in 7,12-dimethylbenz[a] anthracene-induced mammary carcinogenesis in Sprague-Dawley rats. Eur J Pharmacol 2010; 637:22–29.
Lopez-Gonzalez JS, Prado-Garcia H, Aguilar-Cazares D, Molina-Guarneros JA, Morales-Fuentes J, Mandoki JJ. Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin on human lung carcinoma cell lines. Lung Cancer 2004; 43:275–283.
Bronikowska J, Szliszka E, Jaworska D, Czuba ZP, Krol W. The coumarin psoralidin enhances anticancer effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Molecules 2012; 17:6449–6464.
Park B, Oh S, Ahn K, Kwon O, Lee H. (-)-Syringaresinol inhibits proliferation of human promyelocytic HL-60 leukemia cells via G1 arrest and apoptosis. Int Immunopharmacol 2008; 8:967–973.
Bylund A, Saarinen N, Zhang J, Bergh A, Widmark A, Johansson A et al.
Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer. Exp Biol Med 2005; 230:217–223.
Woo KJ, Jeong Y, Park J, Kwon T. Chrysin-induced apoptosis is mediated through caspase activation and Akt inactivation in U937 leukemia cells. Biochem Biophys Res Commun 2004; 325:1215–1222.
Glory MD, Thiruvengadam D. Potential chemopreventive role of chrysin against N
-nitrosodiethylamine-induced hepatocellular carcinoma in rats. Biomed Prev Nutr 2012; 2:106–112.
Tundis R, Deguin B, Loizzo MR, Bonesi M, Statti GA, Tillequin F, Menichini F. Potential antitumor agents: flavones and their derivatives from Linaria reflexa
Desf. Bioorg Med Chem Lett 2005; 15:4757–4760.
Kevan B, Kristina L, Edmund C, Min H, Natale S. EGCG suppresses melanoma tumor angiogenesis and growth without affecting angiogenesis and VEGF expression in the heartand skeletal muscles in mice. J Cancer Res Updates 2014; 3:19–29.
Ying-Qi W, Jian-Liang L, Yue-Rong L, Qing-Sheng L. Suppressive effects of EGCG on cervical cancer. Molecules 2018; 23:2334–2351.
Luo KW, Wei C, Lung WY, Wei XY, Cheng BH, Cai ZM, Huang WR. EGCG inhibited bladder cancer SW780 cell proliferation and migration both in vitro and in vivo via down- regulation of NF-kB and MMP-9. J Nutr Biochem 2017; 14:56–64.
Valeria N, Lleana R, Chiara L, Saverio B, Federica R. Green tea catechins for prostate cancer preventation: present achievements and future challenges. Antioxidants 2017; 6:26.
Heiying J, Wei G, Chunxia Z, Shuiming W. Epigallocatechin gallate inhibites the proliferation of colorectal cancer cells by regulating Notch signaling. Onco Targets Ther 2013; 6:145–153.
Watanabe J, Nishiyama H, Matsui Y, Ito M, Kawanishi H, Kamoto T, Ogawa O. Dicoumarol potentiates cisplatin-induced apoptosis mediated by c-Jun N-terminal kinase in p53 wild-type urogenital cancer cell lines. Oncogene 2006; 25:2500–2508.
Matsui Y, Watanabe J, Ding S, Nishizawa K, Kajita Y, Ichioka K et al.
Dicoumarol enhances doxorubicin-induced cytotoxicity in p53 wild-type urothelial cancer cells through p38 activation. BJU Int 2010; 105:558–564.
Yang J, Xiao Y, He X, Qiu G, Hu X. Aesculetin-induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway in human cervical cancer cells. J Asian Nat Prod Res 2010; 12:185–193.
Ho C, Huang Y, Chen C, Garcinone E, a xanthone derivative, has potent cytotoxic effect against hepatocellular carcinoma cell lines. Planta Med 2002; 68:975–979.
Matsumoto K, Akao Y, Ohguchi K, Ito T, Tanaka T, Iinuma M, Nozawa Y. Xanthones induce cell-cycle arrest and apoptosis in human colon cancer DLD-1 cells. Bioorg Med Chem 2005; 13:6064–6069.
Matsumoto K, Akao Y, Yi H, Ohguchi K, Ito T, Tanaka T et al.
Preferential target is mitochondria in a-mangostin-induced apoptosis in human leukemia HL60 cells. Bioorg Med Chem 2004; 12:5799–5806.
Nakagawa Y, Iinuma M, Naoe T, Nozawa Y, Akao Y. Characterized mechanism of a-mangostin-induced cell death: caspase-independent apoptosis with release of endonuclease-G from mitochondria and increased miR-143 expression in human colorectal cancer DLD-1 cells. Bioorg Med Chem 2007; 15:5620–5628.
Akao Y, Nakagawa Y, Iinuma M, Nozawa Y. Anti-cancer effects of xanthones from pericarps of mangosteen. Int J Mol Sci 2008; 9:355–370.
Wang JJ, Sanderson BJS, Zhang W. Cytotoxic effect of xanthones from pericarp of the tropical fruit mangosteen (Garcinia mangostana
Linn.) on human melanoma cells. Food Chem Toxicol 2011; 49:2385–2391.
Chao A, Hsu Y, Liu C, Kuo P. α−mangostin, a dietary xanthone, induces autophagic cell death by activating the AMP activated protein kinase pathway in glioblastoma cells. J Agric Food Chem 2011; 59:2086–2096.
Kaomongkolgit R, Chaisomboon N, Pavasant P. Apoptotic effect of alpha-mangostin on head and neck squamous carcinoma cells. Arch Oral Biol 2011; 56:483–490.
Korobi M, Shinmoto H, Tsushida T, Shinohara K. Phloretin induced apoptosis in B 16 melanoma 4A5 cells by inhibition of glucose transmembrane transport. Cancer Lett 1997; 19:207–212.
Yang K, Tsai C, Wang Y, Wei P, Lee C, Chen J et al.
Apple polyphenol phloretin potentiates the anticancer actions of Paclitaxel through induction of apoptosis in human Hep G2 cells. Mol Carcinog 2009; 48:420–431.
Cheng S, Liu RH, Sheu J, Chen S, Sinchaikul S, Tsay GJ. Toxicogenomics of A375 human malignant melanoma cells treated with arbutin. J Biomed Sci 2007; 14:87–105.
Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CWW et al.
Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997; 275:218–220.
Hagiwara K, Kosaka N, Yoshioka Y, Takahashi R, Takeshita F, Ochiya T. Stilbene derivatives promote Ago2-dependent tumour-suppressive microRNA activity. Sci Rep 2012; 2:314.
Fulda S, Debatin K. Sensitization for anticancer drug-induced apoptosis by the chemopreventive agent resveratrol. Oncogene 2004; 23:6702–6711.
Chowdhury SA, Kishino K, Satoh R, Hashimoto K, Kikuchi H, Nishiwaka H et al.
Tumor-specificity and apoptosis-inducing activity of stilbenes and flavonoids. Anticancer Res 2005; 25:2055–2064.
Lung HL, Ip WK, Wong CK, Mak NK, Chen ZY, Leung KN. Anti-proliferative and differentiation-inducing activities of the green tea catechin, epigallocatechin-3-gallate (EGCG) on the human eosinophilic leukemia EoL-1 cell line. Life Sci 2002; 72:257–268.
Magyar JÉ, Gamberucci A, Konta L, Margittai É, Mandl J, Bánhehyi G et al.
Endoplasmic reticulum stress underlying the pro-apoptotic effect of epigallocatechin gallate in mouse hepatoma cells. Int J Biochem Cell Biol 2009; 41:694–700.
Ellis LZ, Liu W, Luo Y, Okamoto M, Qu D, Dunn JH, Fujita M. Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1 secretion. Biochem Biophys Res Commun 2012; 414:551–556.
Zhang G, VWang Y, Zhang Y, Wan X, Li J, Liu K et al.
Anti-cancer activities of tea epigallocatechin-3-gallate in breast cancer patients under radiotherapy. Curr Mol Med 2012; 12:163–173.
Hong W, Shengjie B, Chung SY. Green tea polyphenol EGCG suppresses lung cancer cell growth through up regulating miR-210 expression caused by stabilizing HIF-1α. Carcinogenesis 2011; 32:1881–1889.
Suzuki K, Koike H, Matsui H, Ono Y, Hasumi M, Nakazato H et al.
Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCAP and PC-3. Int J Cancer 2002; 99:846–852.
Yanhong H, Peng Y, Qinghong Z, Xiaoyan X. Genistein sensitizes ovarian carcinoma cells to chemotherapy by switching the cell cycle progression in vitro. J Med Coll PLA 2009; 24:125–135.
Sahin K, Tuzcu M, Basak N, Caglayan B, Kilic U, Sahin F, Kucuk O. Sensitization of cervical cancer cells to cisplatin by genistein: the role of NF B and Akt/mTOR signaling pathways. J Oncol 2012; 2012:461562.
Edward M, Jason RG, Daniel RS, Kyung MK, Anthony diSant’ A, Jill K et al.
A phase 2 cancer chemoprevention biomarker trial of isoflavone G-2535 (Genistein) in presurgical bladder cancer patients. Cancer Prev Res (Phila) 2012; 5:621–630.
Lamartiniere CA. Protection against breast cancer with genistein: a component of soy. Am J Clin Nutr 2000; 71:1705S–1707S.
Choi EJ, Kim G. Daidzein causes cell cycle arrest at the G1 and G2/M phases in human breast cancer MCF-7 and MDA-MB-453 cells. Phytomedicine 2008; 15:683–690.
Rabiau N, Kossai M, Braud M, Chalabi M, Satih S, Bignon Y et al.
Genistein and daidzein act on a panel of genes implicated in cell cycle and angiogenesis by polymerase chain reaction arrays in human prostate cancer cell lines. Cancer Epidemiol 2010; 34:200–206.
Guo JM, Xiao BX, Liu DH, Grant M, Zhang S, Lai YF et al.
Biphasic effect of daidzein on cell growth of human colon cancer cells. Food Chem Toxicol 2004; 42:1641–1646.
Shen S, Ko CH, Tseng S, Tsai S, Chen Y. Structurally related antitumor effects of flavanones in vitro and in vivo: involvement of caspase 3 activation, p21 gene expression, and reactive oxygen species production. Toxicol Appl Pharmacol 2004; 197:84–95.
Hsiao Y, Hsieh Y, Kuo W, Chiou H, Yang S, Chinag W, Chu S. The tumor-growth inhibitory activity of flavanone and 2¢-OH flavanone in vitro and in vivo through induction of cell cycle arrest and suppression of cyclins and CDKs. J Biomed Sci 2007; 14:107–119.
Hun MS, Gwang HP, Hyun JE, Jin BJ. Naringenin-mediated ATF3 expression contributes to apoptosis in human colon cancer. Biomol Ther (Seoul) 2016; 24:140–146.
Cvorovic J, Tramer F, Granzotto M, Candussio L, Decorti G, Passamonti S. Oxidative stress-based cytotoxicity of delphinidin and cyanidin in colon cancer cells. Arch Biochem Biophys 2010; 501:151–157.
Hafeez BB, Siddiqui IA, Asim M, Malik A, Afaq F, Adhami VM et al.
A dietary anthocyanidin delphinidin induces apoptosis of human prostate cancer PC3 cells in vitro and in vivo: involvement of nuclear factor-KB signaling. Cancer Res 2008; 68:8564–8572.
Hou DX, Ose T, Lin S, Harazoro K, Imamura I, Kubo M et al.
Anthocyanidins induce apoptosis in human promyelocytic leukemia cells: structure-activity relationship and mechanisms involved. Int J Oncol 2003; 23:705–712.
Li S, Luo X, Li S, Dong M, Xiong L. Effect of hesperidin extraction on cell proliferation and apoptosis of CNE-2Z cells. In: 3rd International Conference on Biomedical Engineering and Informatics; 16–18 October 2010; Yantai, China: IEEE; 2010. pp. 2024–2027.
Márcio C, Isabel CFRF. The role of phenolic compounds in the fight against cancer. Anticancer Agents Med Chem 2013; 13:1236–1258.
Damianaki A, Bakogeorgou E, Kampa M, Notas G, Hatzoglou A, Panagiotou S et al.
Potent inhibitory action of red wine polyphenols on human breast cancer cells. J Cell Biochem 2000; 78:429–441.
Azam S, Hadi N, Khan NU, Hadi SM. Prooxidant property of green tea polyphenols epicatechin and epigallocatechin-3-gallate: implications for anticancer properties. Toxicol In Vitro 2004; 18:555–561.
Ho M, Chen P, Chu S, Kuo D, Kuo W, Chen J, Hsieh Y. Peonidin 3-glucoside inhibits lung cancer metastasis by downregulation of proteinases activities and MAPK pathway. Nutr Cancer 2010; 62:505–516.
Ding M, Feng R, Wang SY, Bowman L, Lu Y, Qian Y et al.
Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity. J Biol Chem 2006; 281:17359–17368.
Chen P, Chu S, Chiou H, Kuo W, Chinag C, Hsieh Y. Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line. Cancer Lett 2006; 235:248–259.
Wang C, Chen L, Yang L. Antitumor activity of four macrocyclic ellagitannins from Cuphea hyssopifolia
. Cancer Lett 1999; 140:195–200.
Wang C, Chen L, Yang L. Cuphiin D1, the macrocyclic hydrolyzable tannin induced apoptosis in HL-60 cell line. Cancer Lett 2000; 149:77–83.
Miyamoto K, Nomura M, Sasakura M, Matsui E, Koshiura R, Murayama T et al.
Antitumor activity of oenothein B, a unique macrocyclic ellagitannin. Jpn J Cancer Res 1993; 84:99–103.
Yegao C, Junju H, Hong Y, Chen Q, Yanli Z, Liqin W et al.
Cytotoxic phenolics from Bulbophyllum odoratissimum
, Food Chem 2008; 107:169–173.
Thanaset S, Somprasong K, Suwatchai M, Jeeranan K, Gulsiri S, Paweena W, Sirinda Y. Phenolic acid composition and anticancer activity against human cancer cell lines of the commercially available fermentation products of Houttuynia cordata
. ScienceAsia 2014; 40:420–427.
Pan MH, Lai CS, Hsu PC, Wang YJ. Acacetin induces apoptosis in human gastric carcinoma cells accompanied by activation of caspase cascades and production of reactive oxygen species. J Agric Food Chem 2005; 53:620–630.
Shim HY, Park JH, Paik HD, Nah SY, Kim DS, Han YS. Acacetin induced apoptosis of human breast cancer MCF-7 cells involves caspase cascade, mitochondria-mediated death signaling and SAPK/JNK1/2-c-Jun activation. Mol Cells 2007; 24:95–104.
Pei-Wen Z, Lien-Chai C, Chun-Ching L. Apigenin induced apoptosis through p53-dependent pathway in human cervical carcinoma cells. Life Sci 2005; 76:1367–1379.
Pidgeon GP, Kandouz M, Meram A, Honn KV. Mechanisms controlling cell cycle arrest and induction of apoptosis after 12-lipoxygenase inhibition in prostate cancer cells. Cancer Res 2002; 62:2721–2727.
Wong BC, Wang WP, Cho CH, Fan XM, Lin MC, Kung HF, Lam SK. 12-lipoxygenase inhibition induced apoptosis in human gastric cancer cells. Carcinogenesis 2001; 22:1349–1354.
So FV, Guthrie N, Chambers AF, Moussa M, Carroll KK. Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutr Cancer 1996; 26:167–181.
Lee JH, Baek NI, Kim SH, Park HW, Yang JH, Lee JJ et al.
A new cytotoxic prenylated chalcone from Sophora flavescens
. Arch Pharm Res 2007; 30:408–411.
Iwashita K, Kobori M, Yamaki K, Tsushida T. Flavonoids inhibit cell growth and induce apoptosis in B16 melanoma 4A5 cells. Biosci Biotechnol Biochem 2000; 64:1813–1820.
Murad LD, Soares Nda C, Brand C, Monteiro MC, Teodoro AJ. Effects of caffeic and 5-caffeoylquinic acids on cell viability and cellular uptake in human colon adenocarcinoma cells. Nutr Cancer 2015; 67:532–542.
Luo M, Liu X, Zu Y, Fu Y, Zhang S, Yao L, Efferth T. Cajanol, a novel anticancer agent from Pigeonpea [Cajanus cajan
(L.) Millsp.] roots, induces apoptosis in human breast cancer cells through a ROS-mediated mitochondrial pathway. Chem Biol Interact 2010; 188:151–160.
Lee HZ, Lin CJ, Yang WH, Leung WC, Chang SP. Aloe-emodin induced DNA damage through generation of reactive oxygen species in human lung carcinoma cells. Cancer Lett 2006; 239:55–63.
Lin ML, Lu YC, Chung JG, Li YC, Wang SG, Wu CY et al.
Aloe-emodin induces apoptosis of human nasopharyngeal carcinoma cells via caspase-8-mediated activation of the mitochondrial death pathway. Cancer Lett 2010; 291:46–58.
Li S, Dong P, Wang J, Gu J, Wu X, Wu W et al.
Icariin, a natural flavonol glycoside, induces apoptosis in human hepatoma SMMC-7721 cells via a ROS/JNK-dependent mitochondrial pathway. Cancer Lett 2010; 298:222–230.
Chow JM, Huang GC, Shen SC, Wu CY, Lin CW, Chen YC. Differential apoptotic effect of wogonin and nor-wogonin via stimulation of ROS production in human leukemia cells. J Cell Biochem 2008; 103:1394–1404.
Chen WY, Hsieh YA, Tsai CI, Kang YF, Chang FR, Wu YC, Wu CC. Protoapigenone, a natural derivative of apigenin, induces mitogen-activated protein kinasedependent apoptosis in human breast cancer cells associated with induction of oxidative stress and inhibition of glutathione S-transferase π. Invest New Drugs 2011; 29:1347–1359.
Xavier CP, Lima CF, Fernandes-Ferreira M, Pereira-Wilson C. Salvia fruticosa, Salvia officinalis, and rosmarinic acid induce apoptosis and inhibit proliferation of human colorectal cell lines: the role in MAPK/ERK pathway. Nutr Cancer 2009; 61:564–571.
[Table 1], [Table 2]