Está en la página 1de 10

∫∑∫“∑¢Õߺ≈‘µ¿—≥±å∏√√¡™“µ‘„π°“√ªÑÕß°—π·≈–√—°…“¡–‡√Áß • Role of Natural Products on cancer Prevention and Treatment

∫∑øóôπøŸ«‘™“°“√ • Review Article

∫∑∫“∑¢Õߺ≈‘µ¿—≥±å∏√√¡™“µ‘„π°“√ªÑÕß°—π·≈–√—°…“¡–‡√Áß
æ‘»¡—¬ ‡À≈à“¿—∑√‡°…¡
¿“§«‘™“‡¿ —™«‘∑¬“ §≥–·æ∑¬»“ µ√å ·≈–
»Ÿπ¬å«‘®—¬æ¬“∏‘„∫‰¡âµ—∫·≈–¡–‡√Áß∑àÕπÈ”¥’ ¡À“«‘∑¬“≈—¬¢Õπ·°àπ

Role of Natural Products on Cancer Prevention and Treatment


Pisamai Luapattarakasem
Department of Pharmacology, Faculty of Medicine; Liver Fluke and Cholangiocarcinoma Research Center,
Khon Kaen University
¡–‡√ÁßÀ√◊Õ‡π◊ÈÕßÕ°™π‘¥√⓬·√ß §◊Õ°âÕπ‚µº‘¥ª°µ‘ (carcinogens) ‡™àπ  “√‡§¡’∫“ß™π‘¥ √—ß ’ À√◊Õ ‰«√—  ·≈–
¢Õ߇π◊ÈÕ‡¬◊ÈÕ∑’ˇ°‘¥®“°°“√·∫àßµ—«¢Õ߇´≈≈åπÕ°‡Àπ◊Õ°“√ √à«¡°—∫§«“¡º‘¥ª°µ‘¢Õß°√–∫«π°“√´àÕ¡·´¡ DNA (DNA re-
§«∫§ÿ¡¢Õß√à“ß°“¬ ·≈– “¡“√∂≈ÿ°≈“¡‰ª¬—߇π◊ÈÕ‡¬◊ËÕ¢â“ß pair) À√◊Õ DNA damage π—Èπ‡°‘¥¡“°‡°‘𧫓¡ “¡“√∂¢Õß
‡§’¬ßÀ√◊Õ°√–®“¬‰ª¬—߇π◊ÈÕ‡¬◊ËÕ·≈–Õ«—¬«–∑’ËÕ¬ŸàÀà“߉°≈ÕÕ° °√–∫«π°“√´àÕ¡·´¡¢Õ߇´≈≈å∑’Ë®–®—¥°“√µ“¡ª°µ‘‰¥â ¡’º≈
‰ª‰¥â ∑”„À⇰‘¥§«“¡º‘¥ª°µ‘µàÕ√à“ß°“¬‰¥â∑—Èß·∫∫‡©æ“– „À⇰‘¥§«“¡º‘¥ª°µ‘¢Õß®’π‡√’¬° initiated cells ´÷ßË initiated cells
∑’Ë (local effect) ®“°°“√°¥‡∫’¬¥¢Õß°âÕπ‡π◊ÈÕµàÕÕ«—¬«–¢â“ß ∑’¡Ë ®’ π’ ∑’ºË ¥‘ ª°µ‘Õ¬Ÿ·à ∫àßµ—«·≈–·æ√à°√–®“¬µàÕÊ ‰ª„π¢—πÈ µÕπ
‡§’¬ßÀ√◊Õ‡°‘¥·∫∫∑—Ë«√à“ß°“¬ (systemic effect) ‡π◊ËÕß®“° ¢Õß promotion ·≈– progression  àߺ≈„Àâ °“√∑”ß“πÀ√◊Õ
°“√·æ√à¢Õ߇´≈≈å¡–‡√Á߉ª¬—ßÕ«—¬«–π—Èπ Ê °“√§«∫§ÿ¡°“√·∫àßµ—«¢Õ߇´≈≈庑¥ª°µ‘·≈–𔉪 Ÿà°“√‡°‘¥
 “‡Àµÿ°“√‡°‘¥¡–‡√Áß æ∫«à“¡’ªí®®—¬√à«¡À≈“°À≈“¬ ¡–‡√Áß„π∑’Ë ÿ¥ √“¬≈–‡Õ’¬¥Õà“π‡æ‘Ë¡‡µ‘¡®“°∫∑ ç°≈‰°°“√
(multifactorial processes) ·≈–ª√–°Õ∫¥â«¬À≈“¬¢—ÈπµÕπ ‡°‘¥¡–‡√Áß∑àÕπÈ”¥’∑’Ë —¡æ—π∏å°—∫°“√µ‘¥æ¬“∏‘„∫‰¡âµ—∫‚¥¬
(multi-stage carcinogenesis) ‰¥â·°à initiation, promotion ·≈– ºà“π∑“ßÕπÿ¡Ÿ≈Õ‘ √–é ·≈– ç “‡Àµÿ·≈–°≈‰°°“√‡°‘¥‚√§¡–
progression (√Ÿª∑’Ë 1)1 „π¢—ÈπµÕπ initiation ®–‡ªìπ°“√°√–µÿâπ ‡√Áß∑àÕπÈ”¥’: ª∞¡∫∑§«“¡ —¡æ—π∏å°—∫欓∏‘„∫‰¡âµ—∫é „π
„À⇰‘¥ DNA damage ∑’ËÕ“®®–‡°‘¥®“°°“√‰¥â√—∫ “√°àÕ¡–‡√Áß ©∫—∫‡¥’¬«°—ππ’È

√Ÿª∑’Ë 1 ·ºπ¿“æ¢Õß multi-stage carcinogenesis1

180 »√’π§√‘π∑√凫™ “√ 2548; 20(3) • Srinagarind Med J 2005; 20(3)


æ‘»¡—¬ ‡À≈à“¿—∑√‡°…¡ • Pisamai Luapattarakasem

°“√√—°…“ ®“°°≈‰°°“√‡°‘¥¡–‡√Áß∑’‡Ë ªìπ multifactor ·≈– °—∫°“√√—°…“·∫∫ combination therapy °Á®–„Àâº≈∑’ˉ¡à¥’π—°


multi-step processes ∑”„Àâ°“√ªÑÕß°—π·≈–√—°…“¡’‰¥âÀ≈“° §«“¡æ¬“¬“¡∑’Ë®–§âπÀ“ “√À√◊Õ¬“∑’Ë„Àâº≈¥’„π°“√√—°…“
À≈“¬ (√Ÿª∑’Ë 2)1, 2 ‡™àπ °“√¬—∫¬—Èß°√–∫«π°“√ initiation ¥â«¬ „π¢≥–∑’ÕË “°“√æ‘…µË”®÷ß¡’§«“¡®”‡ªìπ ‚¥¬‡©æ“–°“√π”¡“
 “√„π°≈ÿ¡à blocking agents Õ“®∑”‰¥â‚¥¬‡æ‘¡Ë °“√∑”ß“π¢Õß „™â„π·ßàªÑÕß°—π/∫√√‡∑“¡–‡√Áß„π√–¬–·√° Ê (√–¬–∑’Ë I, II ´÷Ëß
detoxifying enzyme ‡æ◊ÕË ‡æ‘¡Ë °“√∑”≈“¬ “√ carcinogens À√◊Õ ‡ªìπ√–¬–∑’√Ë °— …“À“¬‰¥â) ®“°√–∫“¥«‘∑¬“∑’æË ∫«à“Õÿ∫µ— °‘ “√≥å
¬—∫¬—Èß oxidative stress ∑’Ë∑”„À⇰‘¥ cell damage ‚¥¬‡©æ“–∑’Ë °“√‡°‘¥¡–‡√Áß∫“ß™π‘¥®–≈¥≈ß„π°≈ÿࡪ√–™“°√∑’ˉ¥â√—∫ “√
DNA ¥â«¬ “√∑’¡Ë ƒ’ ∑∏‘Ï antioxidant À√◊Õscavenging activity ‡™àπ ®“°∏√√¡™“µ‘‰¡à«à“®–‡ªìπæ◊™ º—° À√◊Õ º≈‰¡â 3,4 ∑”„Àâ¡’°“√
ellagic acid, indole-3-carbinol, sulforaphane À√◊Õ flavonoids1 »÷°…“∂÷ß∫∑∫“∑¢Õß “√À√◊Õº≈‘µ¿—≥±å®“°∏√√¡™“µ‘„π°“√
 à«π°“√¬—∫¬—Èß°√–∫«π°“√ promotion À√◊Õ progression ¡—° ªÑÕß°—π·≈–√—°…“¡–‡√Á߇æ‘Ë¡¢÷Èπ5
®–‡°’ˬ«¢âÕß°—∫°“√§«∫§ÿ¡ °“√·∫àßµ—«¢Õ߇´≈≈å„π cell cycle
¢—ÈπµÕπµà“ß Ê À√◊Õ°√–µÿâπ°“√µ“¬¢Õ߇´≈≈å (apoptosis) ¥â«¬ ∫∑∫“∑¢Õߺ≈‘µ¿—≥±å∏√√¡™“µ‘„π°“√ªÑÕß°—π·≈–
 “√„π°≈ÿà¡∑’ˇ√’¬°«à“ suppressing agents ‡™àπ beta-carotene, √—°…“¡–‡√Áß
curcumin, gingerol, epigallocatechin gallate À√◊Õ resveratrol1, 2 ‡ªìπ∑’∑Ë √“∫°—π¥’«“à º≈‘µ¿—≥±å∏√√¡™“µ‘ (natural products)
Õ¬à“߉√°Áµ“¡¬“µâ“π¡–‡√Áß∑’Ë„™â„πªí®®ÿ∫—π°Á¡’¢âÕ®”°—¥‡°’ˬ« ‡ªì π ·À≈à ß ¢Õ߬“∑’Ë  ”§— ≠ ·≈–®“°∑’Ë æ ∫«à “  “√∑’Ë ‰ ¥â ® “°
°—∫º≈¢Õß°“√√—°…“·≈–Õ“°“√æ‘…¢Õ߬“ ª√–°Õ∫°—∫°“√ º≈‘µ¿—≥±å∏√√¡™“µ‘®–¡’À≈“°À≈“¬™π‘¥·≈–∫“ß™π‘¥°Á¡’
µ√«®æ∫¡–‡√Áß¡—°®–‡ªìπ√–¬–À≈—ß Ê ª√–¡“≥°“√«à“√âÕ¬≈– ƒ∑∏‘Ï°«â“ß ∑”„Àâ¡’√“¬ß“πÕ¬à“ß¡“°¡“¬∂÷ß°“√π”‡Õ“
70 ¢ÕߺŸâªÉ«¬¡–‡√Áß∑’ˉ¥â√—∫°“√«‘π‘®©—¬®–¡’°“√·æ√à°√–®“¬ º≈‘µ¿—≥±å∏√√¡™“µ‘¡“„™â„π°“√ªÑÕß°—π √—°…“‚√§µà“ß Ê √«¡
¢Õ߇´≈≈å¡–‡√Áß (metastasis) ·≈â« ´÷Ëß°“√√—°…“·∫∫ local ∑—Èß¡–‡√Áß (µ“√“ß∑’Ë 1)6 Graham ·≈–§≥–7 ‰¥â∑”°“√ ”√«®
treatment (‡™àπ °“√ºà“µ—¥ À√◊Õ°“√©“¬√—ß ’) ®–‰¡à§àÕ¬‰¥âº≈ ®“° NAPRALERT database ®π∂÷ߪï 1999 æ∫«à“¡’√“¬ß“π
°“√√—°…“„π√–¬–π’È®÷ßµâÕß„™â¬“µâ“π¡–‡√Áß (chemotherapy) °“√„™â ¡ÿπ‰æ√æ◊Èπ∫â“π„π°“√√—°…“¡–‡√Áß„πª√–‡∑»µà“ß Ê
´÷ßË ®–¡’º≈‰ª¶à“‡´≈≈å¡–‡√Áß/¬—∫¬—ßÈ °“√·∫àßµ—«¢Õ߇´≈≈å¡–‡√Áß ¡“°¡“¬ ·≈– “√/¬“®“°∏√√¡™“µ‘À≈“¬™π‘¥∑’Ëªí®®ÿ∫—π
®÷ß¡—°®–¡’º≈µàÕ‡´≈≈媰µ‘∑’Ë°”≈—ß·∫àßµ—«‰¥â¥â«¬ ‡™àπ ‡´≈≈å °”≈—ßÕ¬Ÿà√–À«à“ß°“√»÷°…“√–¥—∫§≈‘π‘°‡æ◊ËÕ„™â„π°“√√—°…“
‰¢°√–¥Ÿ° ‡´≈≈å„π∑“߇¥‘πÕ“À“√ À√◊Õ‡´≈≈å∑’Ë√“°º¡ ¡–‡√Áß (µ“√“ß∑’Ë 2-4)6
πÕ°®“°π’ȇ´≈≈å¡–‡√Áß∫“ß™π‘¥®–¡’ªí≠À“°“√¥◊ÈÕ¬“·¡â·µà

√Ÿª∑’Ë 2. ·ºπ¿“æ· ¥ß°≈‰°°“√ÕÕ°ƒ∑∏‘Ï¢Õß “√„π°“√ªÑÕß°—π (blocking agents) ·≈– √—°…“ (suppressing agents) ¡–‡√Áß1

»√’π§√‘π∑√凫™ “√ 2548; 20(3) • Srinagarind Med J 2005; 20(3) 181


∫∑∫“∑¢Õߺ≈‘µ¿—≥±å∏√√¡™“µ‘„π°“√ªÑÕß°—π·≈–√—°…“¡–‡√Áß • Role of Natural Products on cancer Prevention and Treatment

µ“√“ß∑’Ë 1 µ—«Õ¬à“߬“∑’Ëæ—≤π“¡“®“°∏√√¡™“µ‘6

Drug Medical use Mechanism of action Source


Aspirin Analgesic, anti-inflammatory, Inhibition of COX Plant
(Salicylate) antipyretic
Atropine Pupil dilator Antagonist of ACh at muscarinic Plant
receptors at post-ganglionic
parasympathetic neuroeffector sites
Codeine Analgesic, Opioid receptor agonist Plant
antitussive
Digoxin For atrial fibrillation and CHF Inhibition of the Na + /K + ATPase Plant
membrane pump
Morphine Analgesic Opioid receptor agonist Plant
Pilocarpine Glaucoma Muscarinic receptor agonist Plant
Quinine Malaria prophylaxis Inhibition of protein synthesis in the Plant
malaria parasite
Taxol Anticancer agent Antimitotic agent (binds to and stabilizes Plant
microtubules)
Penicillin Antibiotic Inhibition of synthesis of cell wall Microbe
peptidoglycan
Tetracyclin Antibiotic Inhibition of protein synthesis by Microbe
binding to the ribosome 30S subunit
ACh, acetylcholine; CHF, congestive heart failure; COX, cyclooxygenase.

µ“√“ß∑’Ë 2 µ—«Õ¬à“ß “√µâ“π¡–‡√Áß∑’ˉ¥â¡“®“°æ◊™6
Compound Cancer use
Vincristine Leukemia, lymphoma, breast, lung, pediatric solid cancers and others
Vinblastine Breast, lymphoma, germ-cell and renal cancer
Paclitaxel Ovary, breast, lung, bladder, and head and neck cancer
Docetaxel Breast and lung cancer
Topotecan Ovarian, lung and pediatric cancer
Irinotecan Colorectal and lung cancer
Flavopiridol Experimental
Acronyciline Experimental
Bruceantin Experimental
Thalicarpin Experimental

182 »√’π§√‘π∑√凫™ “√ 2548; 20(3) • Srinagarind Med J 2005; 20(3)


æ‘»¡—¬ ‡À≈à“¿—∑√‡°…¡ • Pisamai Luapattarakasem

µ“√“ß∑’Ë 3 µ—«Õ¬à“ß “√µâ“π¡–‡√Áß∑’ˉ¥â¡“®“°‡™◊ÈÕ®ÿ≈‘π∑√’¬6å
Compound Cancer use
Actinomycin Sarcoma and germ-cell tumors
Bleomycin Germ-cell, cervix, and head and neck cancer
Daunomycin Leukemia
Doxorubicin Lymphoma, breast, ovary, lung and sarcomas
Epirubicin Breast cancer
Idarubicin Breast cancer and leukemia
Mitomycin C Gastric, colorectal, anal and lung cancer
Streptozocin Gastric and endocrine tumors
Wortmannin Experimental
Rapamicin* Experimental
Geldanamycin Experimental
*Rapamicin is also a potent immunosupressant.

µ“√“ß∑’Ë 4 µ—«Õ¬à“ß “√µâ“π¡–‡√Áß∑’ˉ¥â¡“®“° —µ«åÀ√◊Õæ◊™®“°∑–‡≈6
Compound Cancer use Mechanism of action
Citarabine Leukemia, lymphoma Inhibition of DNA synthesis
Bryostatin 1 Experimental Activation of PKC
Dolastatin 10 Experimental Inhibition of microtubules and pro-apoptotic effects
Ecteinascidin 743 Experimental Alkylation of DNA
Aplidine Experimental Inhibition of cell-cycle progression
Halicondrin B Experimental Interaction with tubulin
Discodermolide Experimental Stabilization of tubulin
Cryptophycin Experimental Hyperphosphorylation of Bcl-2
PKC, protein kinase C.

„π°“√»÷ ° …“À“º≈‘ µ ¿— ≥ ±å ∏ √√¡™“µ‘ ‡ æ◊Ë Õ ¡“ªÑ Õ ß°— π 燧¡’ªÑÕß°—π¡–‡√Áß : °≈‰°°“√ªÑÕß°—π¢Õ߬“·≈– “√®“°


∫√√‡∑“ √—°…“¡–‡√Áß®–„À⧫“¡ π„®º≈‘µ¿—≥±å∑’Ë¡’ “√∑’Ë ∏√√¡™“µ‘é „π©∫—∫‡¥’¬«°—ππ’È „π∑’Ëπ’È®–¢Õ°≈à“«∂÷ßÀ≈—°°“√
 “¡“√∂ÕÕ°ƒ∑∏‘Ï ‰ ¥â Õ ¬à “ ß°«â “ ߢ«“ß‚¥¬‡©æ“–ƒ∑∏‘Ï ∑’Ë ·≈–µ— « Õ¬à “ ß “√®“°∏√√¡™“µ‘ ¢ Õß “√°≈ÿà ¡ ¥— ß °≈à “ «∑’Ë ¡’
 — ¡ æ— π ∏å °— ∫ °“√‡°‘ ¥ ¡–‡√Á ß ‡™à π ƒ∑∏‘Ï antiinflammatory, √“¬ß“π«à“¡’»—°¬¿“æ„π°“√ªÑÕß°—π/√—°…“¡–‡√Á߇æ◊ËÕ‡ªìπ
antioxidant, immunomodulatory ·≈– cytotoxic activity ´÷Ëß ·π«∑“ß„π°“√π”¡“»÷°…“À“¬“/ “√∑’Ë¡’º≈µàÕ¡–‡√ÁßµàÕ‰ª
„π “¡ƒ∑∏‘Ï·√°®–¡’º≈µàÕ°“√ªÑÕß°—π°“√‡°‘¥¡–‡√Áß„π√–¬–
·√° (initiation phase)  à«πƒ∑∏‘Ï cytotoxicity ®–¡’º≈µàÕ√–¬– 1. Phenolic compounds
promotion ·≈– progression ´÷Ë ß ®–¡’ ƒ ∑∏‘Ï „ π°“√√— ° …“ Phenolic compounds §◊Õ “√∑’ Ë µŸ √‚§√ß √â“ß¡’ OH group
æ∫«à“ “√®“°∏√√¡™“µ‘À≈“¬°≈ÿà¡∑’Ë¡’ƒ∑∏‘Ï¥—ß°≈à“« ‡™àπ ∫π aromatic ring µ—Èß·µà 1 °≈ÿà¡¢÷Èπ‰ª  “√„π°≈ÿà¡π’È®÷ß¡’
phenolic compounds, alkaloids, terperoids, carotenoids ‡ªìπµâπ §ÿ≥ ¡∫—µ∑‘ ®’Ë –≈–≈“¬πÈ”‰¥â¥’ æ∫‰¥â„πæ◊™ º—°·≈– º≈‰¡â∑«—Ë ‰ª
°≈‰°°“√ÕÕ°ƒ∑∏‘Ï „ π√–¥— ∫ ‚¡‡≈°ÿ ≈ Õà “ π‡æ‘Ë ¡ ‡µ‘ ¡ „π∫∑ Õ“®·∫àßÕÕ°‰¥â‡ªìπ 3 °≈ÿà¡„À≠àÊ §◊Õ

»√’π§√‘π∑√凫™ “√ 2548; 20(3) • Srinagarind Med J 2005; 20(3) 183


∫∑∫“∑¢Õߺ≈‘µ¿—≥±å∏√√¡™“µ‘„π°“√ªÑÕß°—π·≈–√—°…“¡–‡√Áß • Role of Natural Products on cancer Prevention and Treatment

(1) Simple phenols/phenolic acid ·≈–Õπÿæ—π∏凙àπ gallic


acid, ellagic acid, tannic acid, vanillin, catechol, resorcinol ·≈–
salicylic acid ‡ªìπµâπ  “√°≈ÿ¡à π’æÈ ∫‰¥â„πº≈‰¡âÀ≈“¬™π‘¥ ‡™àπ
raspberry, blackberry
(2) Phenylpropanoids ‰¥â·°à phenolic compound ∑’Ë
aromatic ring ¡’ three-carbon side chain ‡°“–Õ¬Ÿà ·¬°¬àÕ¬
ÕÕ°‰¥âÀ≈“¬°≈ÿࡉ¥â·°à hydroxycinnamic acids (ferulic acid,
caffeic acid À√◊Õ coumaric acid), coumarins (umbelliferone,
scopoletin, aesculetin À√◊Õ psoralen), lignans (pinoresinol,
eugenol À√◊Õ myristicin) æ∫‰¥â„π ·Õª‡ªî≈ ·æ√å ·≈– °“·ø
(3) Flavonoids ‡ªìπ°≈ÿ¡à  ”§—≠¢Õß phenolic compounds
®–‰¥â·°à “√∑’Ë¡’ Ÿµ√‚§√ß √â“߇ªìπ C6-C3-C6 ·¬°¬àÕ¬ÕÕ°
‰¥â ‡ ªì π À≈“¬°≈ÿà ¡ ‰¥â · °à catechins, proanthocyanins,
anthocyanidins, flavones, flavonols, flavonones ·≈– isoflavones
®“°°“√∑’Ëæ∫ flavonoids ‰¥âÕ¬à“ß°«â“ߢ«“ß∑—Èßæ◊™ º—° º≈‰¡â
√«¡∑—È߇§√◊ËÕߥ◊Ë¡∑’ˇµ√’¬¡¡“®“°æ◊™ ‡™àπ ™“ (µ“√“ß∑’Ë 5)8 ´÷Ëß
æ∫«à“„π„∫™“®–¡’ catechins Õ¬Ÿà∂÷ß 30% ¢ÕßπÈ”Àπ—°·Àâß
·≈–‡™◊ÕË «à“‡ªìπ “√ ”§—≠„π°“√ÕÕ°ƒ∑∏‘‡Ï ªìπ antioxidant ·≈–
chemoprevention Anthocyanins ‡ªìπ “√∑’Ë¡’ ’„πæ◊™  à«π°≈ÿà¡ √Ÿª∑’Ë 3. ·ºπ¿“æ· ¥ß°≈‰°°“√¬—∫¬—Èß°“√‡°‘¥¡–‡√ÁߢÕß
flavones, flavonols ·≈– isoflavones °Á®–æ∫‰¥â∑—Ë«‰ª·≈–‡™◊ËÕ resveratrol11
«à“‡ªìπ “√∑’Ë¡’ª√–‚¬™πåµàÕ√à“ß°“¬8-10
¡’√“¬ß“π∂÷߃∑∏‘™Ï «’ ¿“æ¢Õß phenolic compounds Õ¬à“ß
¡“°¡“¬√«¡∑—È߃∑∏‘ϵâ“π¡–‡√Áß8 ‡™◊ËÕ«à“ƒ∑∏‘ϵâ“π¡–‡√ÁߢÕß ‰¡à§ßµ—«·≈– “¡“√∂∑”„À⇰‘¥ cell damage ‚¥¬°“√‡Àπ’ˬ«
 “√„π°≈ÿà ¡ π’È ® –‡°‘ ¥ ®“° multifunctional activities (¥— ß π”„À⇰‘¥¿“«– oxidative stress ´÷Ëß®–∑”„À⇰‘¥§«“¡º‘¥ª°µ‘
µ—«Õ¬à“ߢÕß resveratrol „π √Ÿª∑’Ë 3)11 ´÷Ëß∑√“∫°—π¥’«à“°≈‰° ¢Õß cell membrane, protein, ·≈– DNA12 ´÷Ë߇™◊ËÕ«à“‡ªìπ°≈‰°
µà“ßʇÀ≈à“π’È¡’ à«π„π°√–∫«π°“√°àÕ¡–‡√Áß ·≈–®–¢Õ°≈à“« ∑’Ë ”§—≠Õ—πÀπ÷ËߢÕß°√–∫«π°“√ carcinogenesis ªí®®ÿ∫—π¡’
∂÷ß°≈‰°¢Õß “√„π°≈ÿࡵà“ß Ê ‚¥¬§√à“«Ê ¥—ßπ’È √“¬ß“π°“√∑¥≈Õ߬◊π¬—π«à“ “√ phenolic compounds À≈“¬
µ—«∑’Ë¡’ƒ∑∏‘Ï antioxidant ·≈–¡’ƒ∑∏‘Ï anticancer ¥â«¬13, 14 „π
Antioxidant activity °√≥’ caffeic, ferulic acid À√◊Õ “√„¥∑’¡Ë §’ «“¡ “¡“√∂∑’®Ë –·¬àß
®“°∑’∑Ë √“∫«à“Õπÿ¡≈Ÿ Õ‘ √– (free radicals) ‰¡à«“à ®–‡ªìπ™π‘¥ (compete) °—∫ electrophile „π°“√®—∫°—∫ DNA ´÷Ëß∂◊Õ‡ªìπ key
reactive oxygen species (ROS: O2-, OH-,H2O2, HOCl) À√◊Õ step ¢Õß°√–∫«π°“√‡°‘ ¥ ¡–‡√Á ß ®–‡√’ ¬ ° “√‡À≈à “ π’È «à “
reactive nitrogen species (RNS: NO, OONO2-) ®–‡ªìπ “√∑’Ë antimutagen 15

µ“√“ß∑’Ë 5. flavonoids ™π‘¥µà“ß Ê ·≈–·À≈àß∑’Ë¡“®“°∏√√¡™“µ‘ 8


Class Typical sources Representative (aglycone)
Flavonols Tea, onions, red wine, fruit Quercetin
Flavones Vegetables, citrus fruits Apigenin
Flavanones Citrus fruit Hesperitin
Anthocyanidins Berries, colored fruit Cyanidin
Catechins Tea, wine Epigallocatechin
Isoflavonoids Legumes Genistein

184 »√’π§√‘π∑√凫™ “√ 2548; 20(3) • Srinagarind Med J 2005; 20(3)


æ‘»¡—¬ ‡À≈à“¿—∑√‡°…¡ • Pisamai Luapattarakasem

Arachidonic acid metabolism modulation stomachs, lung cancer), 4-(methyl-N-nitrosamino)-1-(3-pyridyl)-


 “√∑’Ë¡’ƒ∑∏‘ϵâ“π arachidonic acid metabolism πÕ°®“° 1-butanone (carcinogen „π°“√°√–µÿâπ lung tumor) À√◊Õ N-
®–¡’∫∑∫“∑ ”§—≠„π°“√µâ“π°√–∫«π°“√Õ—°‡ ∫ (antiinflam- nitrosomethylamine (carcinogen ∑’°Ë √–µÿπâ esophageal tumor)28
mation) ·≈â«ªí®®ÿ∫—π¬—߉¥â√—∫§«“¡ π„®„π·ßà°“√ªÑÕß°—π°“√
‡°‘¥¡–‡√Áß (chemoprevention)16, 17 ¡’√“¬ß“π«à“ non-steroidal Immunomodulation
antiinflammatory drugs (NSAIDs) À≈“¬µ—« ‡™àπ sulindac, æ∫«à“ ¡ÿπ‰æ√À√◊Õ “√∑’Ë·¬°®“° ¡ÿπ‰æ√À≈“¬™π‘¥¡’
piroxicam, indomethacin, ·≈– aspirin ¡’ƒ∑∏‘Ϭ—∫¬—Èß°“√‡°‘¥ º≈°√–µÿâπ¿Ÿ¡‘§ÿâ¡°—π ‚¥¬Õ“®®–¡’º≈‡æ‘Ë¡ humoral› À√◊Õ
¡–‡√Áß„π —µ«å∑¥≈Õß∑’Ë∂Ÿ°°√–µÿâπ¥â«¬ “√‡§¡’‚¥¬‡™◊ËÕ«à“Õ“® cell mediated immune response À√◊Õ‡æ‘Ë¡ª√– ‘∑∏‘¿“æ
®–‡π◊ËÕß®“°°“√¬—∫¬—È߇Õπ‰´¡å cyclooxygenase (COX) ´÷Ë߇ªìπ ¢Õß°√–∫«π°“√®— ∫ °‘ π ·≈–¬à Õ ¬∑”≈“¬ ‘Ë ß ·ª≈°ª≈Õ¡
°≈‰°À≈—°¢Õß “√„π°≈ÿà¡ NSAIDs16-19 æ∫«à“ phenolic (phagocytosis)
compounds À≈“¬µ—« ‡™àπ quercetin, eugenol, curcumin ·≈–  “√„π°≈ÿà¡ phenols, quinone À≈“¬™π‘¥∑’Ë¡’ƒ∑∏‘ϵàÕ
green tea ¡’ƒ∑∏‘Ϭ—∫¬—Èß arachidonic acid metabolism ‰¥â √–∫∫¿Ÿ¡‘§ÿâ¡°—π ∫“ß™π‘¥°Á‡æ‘Ë¡ª√‘¡“≥ granulocytes ‡™àπ
‡™àπ°—π·≈–¡’ƒ∑∏‘¬Ï ∫— ¬—ßÈ ∑—ßÈ cyclooxygenase ·≈– lipoxygenase cleisanthin, anethol, catechin, protocatechuic acid, ubiquinone
pathways 20, 21 „πªï 1991, Deschner ·≈–§≥– °Á√“¬ß“π«à“ Q, ∫“ß™π‘ ¥ °Á ‡ æ‘Ë ¡ °“√®— ∫ °‘ π ·≈–¬à Õ ¬®ÿ ≈ ™’ æ ‡™à π 2,3-
quercetin ·≈– rutin ¡’ƒ∑∏‘Ϭ—∫¬—Èß°“√‡°‘¥ colon cancer „π dihydroxybenzoic acid, ferulic acid, curculigoside ®“°«à“πæ√â“«
ÀπŸ∑’Ë∂Ÿ°°√–µÿâπ¥â«¬ azoxymethanol22 ·≈–„πªï 1994 Huang Curculigo orchidoides ∫“ß™π‘¥°Á¡’ƒ∑∏‘Ï°√–µÿâπ„À⇴≈≈å √â“ß
·≈–§≥– √“¬ß“π∂÷߃∑∏‘Ï°“√¬—∫¬—Èß°“√‡°‘¥¡–‡√Áß„π∑“߇¥‘π interferon ´÷Ëß interferon „π¢π“¥µË” Ê ®–°√–µÿâπ°“√ √â“ß
Õ“À“√ (: forestomach, duodenal ·≈– colon) ¢Õß curcumin23 antibody ·≈–°√–µÿâπ macrophage „Àâ∑”≈“¬®ÿ≈™’扥⡓°¢÷Èπ
´÷ßË  Õ¥§≈âÕß°—∫¢âÕ —߇°µ∑’æË ∫«à“ª√–™“°√∑’∫Ë √‘‚¿§Õ“À“√∑’¡Ë ’  “√æ«° phenol & quinone „π°≈ÿà¡π’ȧ◊Õ gossypol ·≈–
phenolic compounds ‡ªìπª√–®”¡’Õÿ∫—µ‘°“√≥å°“√‡°‘¥¡–‡√Áß chlorogenic acid
µË”3, 4  “√„π°≈ÿà¡ saponin ¡—°®–‡ªìπ immunoadjuvants ·µà°Á
¡’ºŸâæ∫«à“ saponin ∫“ß™π‘¥¡’º≈µàÕ°“√¬—∫¬—Èß¡–‡√Áß∫“ß™π‘¥
Enzyme activity modulation ‡™àπ cynanchoside ´÷Ë߇ªìπ steroid-saponin ∑’Ë·¬°‰¥â®“°√“°
„π°√–∫«π°“√‡®√‘≠¢Õ߇´≈≈å®–Õ“»—¬‡Õπ‰´¡åÀ≈“¬ ¢Õß Cyananchum caudatum  “¡“√∂‡æ‘Ë¡°“√®—∫°‘π·≈–
™π‘¥∑’™Ë «à ¬„π°“√‡®√‘≠ (growth) ·≈–°“√·∫àßµ—« (cell division) ¬àÕ¬®ÿ≈™’æ Õπÿæπ— ∏å¢Õß oleanolic acid ®“° Aralia mandshurica
æ∫«à“ phenolic compound À≈“¬™π‘¥ “¡“√∂¬—∫¬—È߇Õπ‰´¡å  “¡“√∂‡æ‘Ë¡ƒ∑∏‘Ï®—∫°‘π·≈–¬àÕ¬®ÿ≈™’æ ¬—∫¬—Èß°“√‡°‘¥¡–‡√Áß
‡À≈à“π’ȉ¥â ∑”„Àâ≈¥ cell hyperproliferation ´÷Ëß¡’º≈≈¥§«“¡ ·≈–ªÑÕß°—π mononuclear system „π —µ«å∑¥≈Õß∑’ˉ¥â√—∫
‡ ’ˬߡ–‡√Á߉¥â µ—«Õ¬à“߇™àπ °“√¬—∫¬—Èß protein kinase C ¢Õß cyclophosphamide
quercetin24, ¬—∫¬—Èß protein tyrosine kinase ¢Õß genistein25, Glycyrrhetinic acid ‡ªìπ triterpene-saponin ∑’ˉ¥â®“°
¬—∫¬—Èß topoisomeraserase ¢Õß psammaplin A15 ·≈–¬—∫¬—Èß ™–‡Õ¡‡∑» (Glycyrrhiza glabra L.) ‰¥â¡’ºŸâ»÷°…“ƒ∑∏‘Ï∑“ß
‡Õπ‰´¡åÀ≈“¬™π‘¥¢Õß green tea26 ‡¿ —™«‘∑¬“À≈“¬Õ¬à“߇™àπ ƒ∑∏‘µÏ “â πÕ—°‡ ∫ µâ“π°“√‡°‘¥·º≈
·≈–µâ“π‰«√—  „πª√–‡∑»≠’˪ÿÉπ„™â “√ °—¥ (glycyrrhizin) √à«¡
Inhibition of carcinogen formation °—∫ glycine ·≈– cysteine „π°“√√—°…“µ—∫Õ—°‡ ∫ ·≈–ƒ∑∏‘Ï
 “√ carcinogens ‡ªìπªí®®—¬Àπ÷ßË ∑’‡Ë √àß„À⇰‘¥¡–‡√Áß ·À≈àß µàÕ√–∫∫¿Ÿ¡‘§ÿâ¡°—π Abe ·≈–§≥–29 ‰¥âæ∫«à“ glycyrrhitinic
¢Õß carcinogen ∑’Ë¡πÿ…¬å‰¥â√—∫®–¡’∑—Èß exogenous ·≈– acid ·≈– glycyrrhizin  “¡“√∂‡Àπ’ˬ«π”„Àâ‡æ‘Ë¡ interferon „π
endogenous sources °“√À≈’°‡≈’ˬߠ“√ carcinogen ®“° ÀπŸ∂’∫®—°√‡¡◊ËÕ„Àâ„π¢π“¥ 20 ·≈– 50 mg/kg. °“√∑¥≈Õß
¿“¬πÕ°À√◊Õ≈¥°“√ √â“ß “√ carcinogen „π√à“ß°“¬ ®–™à«¬ ∑“ߧ≈‘π‘°æ∫«à“ ‡¡◊ËÕ©’¥ glycyrrhizin ¢π“¥ 80 mg. ®–∑”„Àâ
≈¥Õÿ∫—µ‘°“√≥å°“√‡°‘¥¡–‡√Á߉¥â æ∫«à“ phenolic compounds ºŸªâ «É ¬¡’ interferon ‡æ‘¡Ë ¢÷πÈ 45% „πºŸªâ «É ¬ 21 √“¬ ·≈–¬—߇ √‘¡
À≈“¬µ—«¡’ƒ∑∏‘Ϭ—∫¬—Èß°“√ √â“ß “√ carcinogens „π√à“ß°“¬‰¥â ƒ∑∏‘Ï¢Õß NK cell ‰¥â¥â«¬
‡™àπ °“√¬—∫¬—Èß°√–∫«π°“√ nitrosation ¢Õß caffeic ·≈– πÕ°®“°°“√»÷°…“ in vitro ¥—߉¥â°≈à“«¡“·≈â« ¬—ß¡’
ferulic acid27 À√◊Õ°“√¬—∫¬—ßÈ nitrosation „πÀπŸ∑ªË’ ÕÑ π¥â«¬ green √“¬ß“π„π in vivo Õ’°¡“°¡“¬∑’Ë· ¥ß∂÷ߺ≈¢Õß phenolic
tea ¡’º≈„Àâ≈¥Õÿ∫µ— °‘ “√≥å°“√‡°‘¥¡–‡√ÁßÀ≈“¬™π‘¥ ‡™àπ ≈¥°“√ compound „π°“√¬—∫¬—Èß°“√‡°‘¥¡–‡√Áß ®–¢Õ°≈à“«∂÷߇©æ“–
 √â“ß N-nitrosodiethylamine (carcinogen ∑’Ë°√–µÿâπ„À⇰‘¥ fore  “√∑’Ëæ∫‰¥â∫àÕ¬ ‡™àπ

»√’π§√‘π∑√凫™ “√ 2548; 20(3) • Srinagarind Med J 2005; 20(3) 185


∫∑∫“∑¢Õߺ≈‘µ¿—≥±å∏√√¡™“µ‘„π°“√ªÑÕß°—π·≈–√—°…“¡–‡√Áß • Role of Natural Products on cancer Prevention and Treatment

Quercetin ·≈– rutin ‡ªìπ phenolic compound ∑’Ëæ∫‰¥â ‡¿ —™«‘∑¬“¢Õß alkaloids °Á¡’√“¬ß“πÕ¬à“ß°«â“ߢ«“ß∑—Èß
∫àÕ¬„π human food æ∫«à“ÀπŸ∑’Ë∑“¥â«¬ quercetin/rutin ®–¡’ antioxidant 45, antiinflammatory46 ·≈– inhibit enzyme activity
º≈¬—∫¬—Èß°“√‡°‘¥¡–‡√Áß∑’˺‘«Àπ—ß∑’Ë°√–µÿâπ¥â«¬ phorbal ester ‡™à𠇪ìπ potent protein kinase C inhibitor47, topoisomerase
(TPA)30 À√◊Õ°“√∑¥≈Õß„ÀâÀπŸ√—∫ª√–∑“πÕ“À“√∑’˺ ¡¥â«¬ inhibitor42 ƒ∑∏‘ϵàÕ√–∫∫¿Ÿ¡‘§ÿâ¡°—π®–‡æ‘Ë¡ª√– ‘∑∏‘¿“æ¢Õß
quercetin ®–¬—∫¬—Èß°“√°√–µÿâπ„À⇰‘¥¡–‡√Áß∑’ˇµâ“π¡ (°√–µÿâπ °√–∫«π°“√®—∫°‘π·≈–¬àÕ¬∑”≈“¬®ÿ≈™’æ ‡™àπ aristolochic
¥â«¬ DMBA+NMU)31 ·≈–¡–‡√Áß≈”‰ â (°√–µÿπ⠥⫬ AOM)32 ‰¥â acid ∑’Ë·¬°‰¥â®“° Aristolochia elematitis ®–¡’º≈‡æ‘Ë¡
Curcumin ( “√ ’‡À≈◊Õß∑’æË ∫‰¥â„πæ◊™À≈“¬™π‘¥ ‡™àπ ‡Àßâ“ phagocytosis ¢Õß lymphocytes ·≈– peripheral macrophage
¢Õߢ¡‘Èπ™—π, Curcuma longa) æ∫«à“¡’ƒ∑∏‘Ï antiinflammatory ·≈– aristolochic acid „π¢π“¥ 5 µg /kg ®– “¡“√∂µâ“π
(mouse ear test) ·≈–¡’ strong antitumorigenic activity „π ƒ∑∏‘°Ï “√°¥¿Ÿ¡§‘ ¡âÿ °—π¢Õß prednisolone ‰¥â πÕ°®“°π’°È “√‡æ‘¡Ë
 —µ«å∑¥≈Õß∑’°Ë √–µÿπ⠥⫬ DMBA À√◊Õ TPA ∑”„Àâ≈¥Õÿ∫µ— °‘ “√≥å phagocytosis ¬—ßæ∫‰¥â°—∫ isopteropodine (alkaloid ∑’Ë·¬°‰¥â
°“√‡°‘¥ gastric, duodenal ·≈– colon carcinogenesis33 ®“° Uncaria tomentosa), ·≈– Vincristine (alkaloid ∑’Ë·¬°‰¥â
Caffeic ·≈– Ferulic acid ( “√∑’Ëæ∫‰¥â„πº—°·≈–º≈‰¡â ®“° Catharanthus roseus)  à«πƒ∑∏‘ϵâ“π¡–‡√ÁߢÕß alkaloids
À≈“¬™π‘¥) ∑—Èß caffeic ·≈– ferulic acid ®–¡’º≈¬—∫¬—Èß°“√‡°‘¥ πÕ°®“°ƒ∑∏‘Ï antiproliferation40, 47 ·≈â« alkaloids À≈“¬µ—«∑’Ë
chemical-induced forestomach tumor „πÀπŸ∂’∫®—°√26 ·≈– πÕ°®“°®–¡’ƒ∑∏‘Ï cytotoxic48,49 ‚¥¬µ√ß·≈⫇¡◊ËÕ„Àâ√à«¡°—∫
caffeic ¡’ƒ∑∏‘χªìπ potent inhibitor ¢Õß°“√ √â“ß carcinogenic ¬“µâ“π¡–‡√Áßµ—«Õ◊πË °Á®–™à«¬≈¥Õ“°“√æ‘…¢Õ߬“ conventional
nitrosamines34 anticancer ‰¥â ‡™àπ swainsonine ®–™à«¬≈¥Õ“°“√æ‘…µàÕ
Ellegic acid (æ∫‰¥â„π walnuts, raspberries ·≈–º≈‰¡âÕ’° ‰¢°√–¥Ÿ°¢Õß methotrexate, 5-fluorouracil, cyclophosphamide,
À≈“¬™π‘¥) æ∫«à“¡’ƒ∑∏‘Ϭ—∫¬—Èß chemical-induced esophageal, ·≈– doxorubicin ‰¥â50 À√◊Õ‡°‘¥ synergistic effect ‰¥â ‡™àπ°“√
lung, liver carcinogenesis35 „Àâ vinflunine À√◊Õ vinorelbine (°≈ÿà¡ vinka alkaloid) √à«¡°—∫
cisplatin, mitomycin C, doxorubicin À√◊Õ 5-fluorouracil44
2. Lignans πÕ°®“°π’È°“√„Àâ alkaloids ∫“ß™π‘¥‡™àπ cepharanthin À√◊Õ
Lignans ®—¥‡ªìπ°≈ÿà¡Àπ÷ËߢÕß phenolic compound (°≈ÿà¡ tetrandrine ®–™à«¬≈¥Õ“°“√¥◊ÈÕ¬“µàÕ conventional drug ∫“ß
phenylpropanoids) ¡’√“¬ß“π∂÷ß cytotoxicity property ¢Õß lignan ™π‘¥‰¥â ‚¥¬®–‰ª¡’º≈µâ“π°“√¢—∫¬“ÕÕ°®“°‡´≈≈å ‚¥¬°“√
∑—ßÈ in vitro36 ·≈– in vivo37 µàÕ¡“¡’°“√§âπæ∫ podophyllotoxins, ÕÕ°ƒ∑∏‘Ï∑’Ë p-glycoprotein 51, 52
 “√∑’Ë·¬° °—¥‰¥â®“°µâπ Mayapple (Podophyllum peltatum),
¡’ƒ∑∏‘Ϭ—∫¬—Èß°“√∑”ß“π¢Õß microtubule ·≈–®“°°“√∑¥≈Õß 4. Diterpenoids
µàÕÊ ¡“æ∫«à“ “√°÷Ëß —߇§√“–Àå¢Õß podophyllotoxin ‡™àπ Diterpenoids ‡ªìπ°≈ÿà¡Àπ÷ËߢÕß terpenoids ´÷Ë߇ªìπ “√
etoposide À√◊Õ teniposide ®–¡’ƒ∑∏‘ϵâ“π¡–‡√Áß∑’Ë ”§—≠ °≈ÿà¡„À≠àÕ’°°≈ÿà¡Àπ÷Ëß∑’Ëæ∫„πæ◊™ √â“ß¡“®“°°“√√«¡µ—«¢Õß
ªí®®ÿ∫—π etoposide „™â‡ªìπ¬“√—°…“¡–‡√ÁßÀ≈“¬™π‘¥‚¥¬ isoprene molecule CH2=C(CH3)-CH=CH3 (C5 unit) µ—ßÈ ·µà 2 °≈ÿ¡à
‡©æ“–¡–‡√Áß∑’Ë¥◊ÈÕ¬“ ‡™àπ testicular carcinoma, small-cell lung ¢÷πÈ ‰ª „π°√≥’¢Õß diterpenoids °Á®–‡°‘¥®“°°“√√«¡°≈ÿ¡à ¢Õß
carcinoma, nonlymphocytic leukemic ·≈– non-Hodgkinûs isoprene 4 units (C20)
lymphomas38 Taxol (paclitaxel) ‡ªìπ diterpenoid ∑’Ë·¬°‰¥â®“°‡ª≈◊Õ°
¢Õßµâπ yew tree (Taxus brevifolia) ¡’√“¬ß“π∂÷߃∑∏‘ϵâ“π
3. Alkaloids ¡–‡√ÁßÀ≈“¬™π‘¥ ‡™àπ ovarian ·≈– breast cancer, malignant
Alkaloids ‡ªìπ “√Õ’°°≈ÿà¡Àπ÷Ëß∑’Ëæ∫¡“°„πæ◊™·≈–æ∫«à“ melanoma ·≈– acute myclogenous leukemia „π°“√»÷°…“
‡ªìπ “√∑’Ë¡—°®–¡’æ‘…·≈–¡’ƒ∑∏‘Ï∑“߇¿ —™«‘∑¬“Õ¬à“ß°«â“ß „π√–¥—∫ phase II ‚¥¬„Àâ√à«¡°—∫ dexamethasone, diphenhy-
¢«“ß  “√„π°≈ÿ¡à π’®È –¡’ µŸ √‚§√ß √â“ß∑’·Ë µ°µà“ß°—π¡“°∑”„Àâ dramine (‡æ◊ËÕ≈¥ allergic reaction) „π°“√√—°…“ ovarian
¬“°∑’Ë®–„À⧔®”°—¥§«“¡ ·µàÕ¬à“߉√°Áµ“¡‚¥¬∑—Ë«‰ª·≈â« cancer ‚¥¬‡©æ“–°≈ÿà¡∑’Ë¥◊ÈÕ¬“53, 54
alkaloids ¡—°®–‡ªìπ “√∑’‰Ë ¡à¡ ’ ’ ¡’ƒ∑∏‘‡Ï ªìπ¥à“ß ·≈–¡’ nitrogen
atom ‡ªìπ à«πª√–°Õ∫¢Õß cyclic part  √ÿª
¡’√“¬ß“π∂÷߃∑∏‘ϵâ“π¡–‡√ÁߢÕß “√„π°≈ÿà¡ alkaloids ¡–‡√Á߇ªìπªí≠À“ ÿ¢¿“æ¢Õߪ√–™“°√„πªí®®ÿ∫—π·≈–¡’
Õ¬Ÿà¡“°¡“¬39-42 ·≈–À≈“¬µ—«Õ¬Ÿà√–À«à“ß°“√»÷°…“√–¥—∫ Õ—µ√“∑’ˇæ‘Ë¡¢÷Èπ °“√√—°…“ (‚¥¬‡©æ“–¡–‡√Áß„π√–¬–∑⓬ Ê)
§≈‘ π‘ ° 42-44 ‡™à 𠇥’ ¬ «°— ∫ phenolic compound ƒ∑∏‘Ï ∑ “ß ¬ÿà ß ¬“°¥â « ¬¢â Õ ®”°— ¥ ¢ÕßÕ“°“√æ‘ … ¢Õ߬“·≈–°“√¥◊È Õ ¬“

186 »√’π§√‘π∑√凫™ “√ 2548; 20(3) • Srinagarind Med J 2005; 20(3)


æ‘»¡—¬ ‡À≈à“¿—∑√‡°…¡ • Pisamai Luapattarakasem

‡π◊ËÕß®“°°“√‡°‘¥¡–‡√Áß¡’À≈“¬¢—ÈπµÕπ·≈–§àÕ¬‡ªìπ§àÕ¬‰ª 11. Pervaiz S. Chemotherapeutic potential of the chemopreven-

„π√–¬–·√° Ê ∑”„Àâ°“√ªÑÕß°—π°“√‡°‘¥¡–‡√Áß¡’°“√»÷°…“ tive phytoalexin resveratrol. Drug Resistance Updates 2004;


5: 333-44.
°— π Õ¬à “ ß·æ√à À ≈“¬‚¥¬‡©æ“–°“√„™â   “√À√◊ Õ º≈‘ µ ¿— ≥ ±å 12. Pacifici R, Davies J. Protein, lipid, and DNA repair systems
∏√√¡™“µ‘ ªí®®ÿ∫—π¡’√“¬ß“π¬◊π¬—π∂÷߃∑∏‘ϵà“ß Ê ∑’˙૬„π in oxidative stress: the free-radical theory of aging revisited.
°“√ªÑÕß°—π°“√‡°‘¥¡–‡√Á߉¥â πÕ°®“°π’ È “√‡À≈à“π’ÀÈ ≈“¬™π‘¥ Gerontology 1991; 37: 166-80.
¬—ß “¡“√∂„™â‡ √‘¡ƒ∑∏‘Ϭ“µâ“π¡–‡√Áß ∑”„Àâ≈¥°“√¥◊ÈÕ¬“ 13. Premalantha B, Sachdanandam P. Semecarpus anacardium
·≈–≈¥¢π“¥¢Õ߬“‰¥â ∑”„ÀâÕ“°“√¢â“߇§’¬ß¢Õ߬“≈¥≈ß L. nut extract administration induces the in vivo antioxidant
defence system in aflatoxin B1 mediated hepatocellular
 “√À√◊Õº≈‘µ¿—≥±å∏√√¡™“µ‘‡À≈à“π’È à«π„À≠à¡’°“√„™â‡ªìπ
carcinoma. J Ethnopharmacol 1999; 66: 131-9.
‡§√◊ËÕߥ◊Ë¡·≈–Õ“À“√„πª√–™“°√„π∑«’ª‡Õ‡™’¬´÷Ëß Õ¥§≈âÕß 14. Owen R, Giacosa A, Hull W, Haubnwe R, Spiegelhalder B,
°—∫Õÿ∫—µ‘°“√≥å°“√‡°‘¥¡–‡√Áß∫“ß™π‘¥„πª√–™“°√‡À≈à“π’ȵ˔ Bartsch H. The antioxidant/anticancer potential of phenolic
°«à “ „π°≈ÿà ¡ ª√–™“°√„π·∂∫µ–«— π µ°∑’Ë ¡’ ° “√∫√‘ ‚ ¿§ “√ compounds isolated from olive oil. Eur J Cancer 2000;
‡À≈à“π’ȵ˔ πÕ°®“°ƒ∑∏‘Ï¥—ß°≈à“«¢â“ßµâπ·≈â«  “√‡À≈à“π’Ȭ—ß 36:1235-47.

¡’ƒ∑∏‘Ï°«â“ߢ«“ß·≈–¡’§«“¡‡ªìπæ‘…µË” ®÷߇À¡“–∑’Ë®–»÷°…“ 15. Kim D, Lee I, Jung J, Lee C, Choi S. Psammaplin A, a


natural phenolic compound, has inhibitory effect on human
‡æ◊ËÕπ”¡“„™â„π°“√ªÑÕß°—π°“√‡°‘¥¡–‡√Áß
topoisomerase II and is cytotoxic to cancer cells.
Anticancer-Res 1999; 19(5B):4085-90.
‡Õ° “√Õâ“ßÕ‘ß 16. Brown JR, DuBois RN. COX-2: a molecular target for
1. Surh YJ. Molecular mechanisms of chemopreventive effects colorectal cancer prevention. J Clin Oncol 2005; 23:
of selected dietary and medicinal phenolic substances. 2840-55.
Mutation Research 1999; 428: 305-27. 17. Wang Z. The role of COX-2 in oral cancer development, and
2. Chen C, Kong ANT. Dietary chemopreventive compounds chemoprevention/ treatment of oral cancer by selective
and ARE/EpRE signaling. Free Radical & Medicine 2004; COX-2 inhibitors. Curr Pharm Des 2005; 11: 1771-7.
36: 1505-16. 18. Peek RM, Jr. Prevention of colorectal cancer through the
3. Jolly CA. Diet manipulation and prevention of aging, cancer use of COX-2 selective inhibitors. Cancer Chemother
and autoimmune disease. Curr Opin Clin Nutr Metab Care Pharmacol 2004; 54 Suppl 1:S50-6.
2005; 8: 382-7. 19. Harris RE, Beebe-Donk J, Doss H, Burr Doss D. Aspirin,
4. Mentor-Marcel R, Lamartiniere CA, Eltoum IA, Greenberg ibuprofen, and other non-steroidal anti-inflammatory drugs
NM, Elgavish A. Dietary genistein improves survival and in cancer prevention: a critical review of non-selective
reduces expression of osteopontin in the prostate of COX-2 blockade (review). Oncol Rep 2005; 13: 559-83.
transgenic mice with prostatic adenocarcinoma (TRAMP). J 20. Rao C, Rivenson A, Simi B, Reddy B. Chemoprevention of
Nutr 2005; 135: 989-95. colon carcinogenesis by dietary curcumin, a naturally
5. Chen C, Kong ANT. Dietary cancer-chemopreventive occurring plant phenolic compound. Cancer Res 1995; 55:
compounds: from signaling and gene expression to 259-66.
pharmacological effects. Trends in Pharmacological Sciences 21. Kohyama N, Nagata T, Fujimoto S, Sekiya K. Inhibition of
2005; 26: 318-26. arachidonate lipoxygenase activities by 2-(3,
6. da Rocha AB, Lopes RM, Schwartsmann G. Natural 4-dihydroxyphenyl) ethanol, a phenolic compound from
products in anticancer therapy. Current Opinion in olives. Biosci Biotechnol Biochem 1997; 61: 347-50.
Pharmacology 2001; 1: 364-9. 22. Deschner E, Ruperto J, Wong G, Newmark H. Quercetin
7. Graham JG, Quinn ML, Fabricant DS, Farnsworth NR. Plants and rutin as inhibitors of azoxymethanol-induced colonic
used against cancer-an extension of the work of Jonathan neoplasia. Carcinogenesis 1991; 12: 1193-6.
Hartwell. J Ethnopharmacol 2000; 73: 347-77. 23. Huang M, Lou Y, Ma W, Newmark H, Reuhl K, Conney A.
8. Hertog MGL, Katan MB. Quercetin in foods, cardiovascular Inhibitory effects of dietary curcumin on forestomach,
disease, and cancer. New York: Marcel Dekker; 1998. duodenal and colon carcinogensis in mice. Cancer Res
9. Newmark HL. Plants phenolics as potential cancer 1994; 54: 5841-7.
prevention agents. New York: Plenum Press; 1996. 24. Schwartz B, Fraser G, Levy J, Sharoni Y, Guberman R,
10. Agarwal R, Mulkhtar H. Cancer chemoprevention by Krawiec J, et al. Differential distribution of protein kinase along
polyphenols in green tea and artichoke. New York: Plenum the crypt-to-lumen regions of rat colonic epithelium. Gut 1988;
Press; 1996. 29: 1213-21.

»√’π§√‘π∑√凫™ “√ 2548; 20(3) • Srinagarind Med J 2005; 20(3) 187


∫∑∫“∑¢Õߺ≈‘µ¿—≥±å∏√√¡™“µ‘„π°“√ªÑÕß°—π·≈–√—°…“¡–‡√Áß • Role of Natural Products on cancer Prevention and Treatment

25. Akiyama T, Isida J, Nakagawa S, Ogawara H, Watanabe S, 39. Ye Z, Sun A, Li L, Cao X, Ye W. Reveral of adriamycin or
Itoh N, et al. Genistein, a specific inhibitor of tyrosine- vincristine resistance by tetrandrine in human cancer cells
specific protein kinases. J Biol Chem 1987; 262: 5592-5. in vitro. Chung Kuo Chung Yao Tsa Chih 1996; 21: 369-71,
26. Ho CT, Ferraro T, Chen Q, Rosen RT, Huang MT. 384.
Phytochemicals in teas and rosemary and their cancer- 40. Kang T, Pae H, Yoo J, Kim N, Kim Y, Ko G, et al.
preventive properties. Washington, DC: American Chemical Antiproliferative effects of alka;oids from Sedum
Society; 1994. sarmentosum on murine and human hepatoma cell lines.
27. Kuenzig W, Chang J, Norkus E, Holowaschenko H, Newmark J Ethnopharmacol 2000; 70: 177-82.
H, Mergens W, et al. Caffeic and ferulic acid as blockers of 41. Minuzzo M, Marchini S, Broggini M, Faircloth G, D’lncalci M,
nitrosamine formation. Carcinogenesis 1984; 5: 309-13. Mantovani R. Interference of transcriptional activation by the
28. Wang ZY, Hong JY, Huang MT, Reuhl KR, Conney AH, Yang antineoplastic drug ecteinascidin-743. Proc Natl Acad
CS. Inhibition of N-nitrosodiethylamine- and Sci USA 2000; 97: 6780-4.
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced 42. Zhang R, Li Y, Cai Q, Liu T, Sun H, Chambless B. Preclinical
tumorigenesis in A/J mice by green tea and black tea. pharmacology of the natural product anticancer agent
Cancer Res 1992; 52: 1943-7. 10-hydroxycamptothecin, an inhibitor of topoisomerase I.
29. Abe N, Ebina T, Ishida N. Interferon induction by glycyrrhizin Cancer chemother Pharmacol 1998; 41: 257-67.
and glycyrrhetinic acid in mice. Mikrobiol Immuno 1982; 26: 43. Bannach R, Valenzuela A, Cassels B, Nunez V, LJ., Speisky
535-9. H. Cytoprotective and antioxidant effects of boldine on
30. Kato R, Nakadate T, Yamamoto S, Sugimura T. Inhibition of tert-butyl hydroperoxide-induced damage to isolated
12-0-tetradecanoylphorbol-13-acetate induced tumor hepatocytes. Cell Biol Toxicol 1996; 12: 89-100.
promotion and ornithine decarboxylase activity by 44. Barret J, Etievant C, Hill B. In vitro synergistic effects of
quercetin: possible involvement by lipoxygenase inhibition. vinflunine, a novel fluorinated vinca alkaloid, in combination
Carcinogenesis 1983; 4: 1301-5. with other anticancer drugs. Cancer chemother Pharmacol
31. Verma A, Johnson J, Gould M, Tanner M. Inhibition of 7, 2000; 45: 471-6.
12-dimethylbenz(a)anthracene and N-nitrosomethylurea- 45. Shi X, Mao Y, Saffiotti U, Wang L, Rojanasakul Y, Leonard
induced rat mammary cancer by dietary flavonol quercetin. S, et al. Antioxidant activity of tetrandrine and its inhibition of
Cancer Res 1988; 20: 199-204. quartz-induced lipid peroxidation. J Toxicol Environ Health
32. Deschner E, Ruperto J, Wang Z, Newmark H. The effect of 1995; 46: 233-48.
dietary quercetin and rutin on AOM-induced acute colonic 46. Blaghen N, Lahlou N, Dzairi F, Moutaouakkil A, Talbi M.
epithelial abnormalities in mice fed a high-fat diet. Nutr Complexation and ionophoric properties of taxol and
Cancer 1993; 20: 199-204. colchicine: complex formation and transport of sodiam,
33. Huang M, Robertson F, Lysz T, Ferraro T, Wang Z, Georgiadis potassium, magnesium and calcium ions across a liquid
C, et al. Inhibitory effects of curcumin on carcinogenesis in membrane. Nat Toxins. 1999; 7: 179-85.
mouse epidermis. Antioxidants and Cancer Prevention 47. Caponigro F, French R, Kaye S. protein kinase C: a worth-
Society 1992: 339-49. while targer for anticancer drugs? Anticancer Drugs. 1997;
34. Wattenberg L, Cocciaa J, Lam L. Inhibitory effects of phe- 8: 26-33.
nolic compounds on benzo(a)pyrene induced neoplasia. 48. Fridborg H, Nygren P, Dhar S, Csoka K, Kristensen J, Larsson
Cancer Res 1990; 40: 2820-3. R. In vitro evaluation of new anticancer drugs, exemplified
35. Lesca P. Protective effects of ellagic acid and other plant by vinorelbine, using the fluorometric microculture cytotox-
phenols on benzo(a)pyrene-induced neoplasia in mice. icity assay on human tumor cell lines and patient biopsy cells.
Carcinogenesis 1983; 6:1651-3. J Exp Ther Oncol 1996; 1: 286-95.
36. Middel O, Woerdenbag H, van-Uden W, van-Oeveren A, 49. Pauwels O, Kiss R, Pasreels J, Atassi G. Cytotoxicity, cell
Jansen J, Feringa B, et al. Synthesis and cytotoxicity of novel cycle kinetics and morphonuclear-induced effects of Vinca
lignans. J Med Chem 1995; 38: 2112-8. alkaloid anticancer agents. J Pharm Pharmacol. 1995; 47:
37. Thompson L, Rickard S, Cheung F, Kenaschuk E, Obermeyer 870-5.
W. Variability in anticancer lignan levels in flaxseed. 50. Oredipe O, White S, Grzegorzewski K, Gause B, Cha J, Miles
Nutr Cancer 1997; 28: 26-30. V, et al. Protective effects of swainsonine in murine survival
38. Imbert T. Discovery of podophyllotoxins. Biochimie 1998; and bone marrow proliferation during cytotoxic chemo-
80: 207-22. therapy. J Natl Cancer Inst. 1991; 83: 1149-56.

188 »√’π§√‘π∑√凫™ “√ 2548; 20(3) • Srinagarind Med J 2005; 20(3)


æ‘»¡—¬ ‡À≈à“¿—∑√‡°…¡ • Pisamai Luapattarakasem

51. Hirai M, Tanaka K, Shimizu T, Tanigawara Y, Yasuhara M, 53. Wilson L, Jordan MA. New microtubule/tubulin-targeted
Hori R, et al. Cepharanthin, a multidrug resistant modifier, is anticancer drugs and novel chemotherapeutic strategies. J
a substrate for P-glycoprotein. J Pharmacol Exp Ther. Chemother 2004; 16 Suppl 4: 83-5.
1995; 275: 73-8. 54. Zhao J, Kim JE, Reed E, Li QQ. Molecular mechanism of
52. Choi S, Park S, Kim K, Choi E, Kim S, Park W, et al. The antitumor activity of taxanes in lung cancer. Int J Oncol
bisbenzylisoquinoline alkaloids, tetrandine and fangchinoline, 2005;27:247-56.
enhance the cytotoxicity of multidrug resistance-ralated drugs
via modulation of P-glycoprotein. Anticancer-Drugs. 1998;
9: 255-61.

»√’π§√‘π∑√凫™ “√ 2548; 20(3) • Srinagarind Med J 2005; 20(3) 189