Pharmacy Perspectives - Fall 2011 - 4

F A C u Lt y

Resveratrol	in	Red	Wine	 Selectively	Kills		 Cancer	Cells
By Garth Sundem

Resveratrol,	a	chemical	found	in	red	wine	and	peanuts,	 exploits	a	genetic	difference	between	healthy	and	cancerous	cells	in	head	and	neck	tumors	to	selectively	kill	 the	cancerous	cells	while	leaving	healthy	cells	unharmed. “This	is	a	major	breakthrough	kind	of	thing,”	says		 Rajesh	Agarwal,	PhD,	professor	of	pharmaceutical		 sciences	at	the	School	of	Pharmacy	and	investigator		 at	the	University	of	Colorado	Cancer	Center,	who	 partnered	on	the	study	with	Robert	Sclafani,	also	of	the		 Cancer	Center	and	professor	of	biochemistry	and	molecular	 genetics	at	the	School	of	Medicine. The	way	it	works	is	this:	in	both	healthy	and	cancerous	cells,	cell	division	takes	place	in	 three	phases.	During	the	middle	phase	–	S-phase	–	the	cell	makes	a	copy	of	its	DNA	that	 will	then	build	the	new	cell.	As	you	might	guess,	accurate	replication	of	this	DNA	is,	as	 Martha	Stewart	would	say,	a	good	thing	–	healthy	cells	have	extensive	repair	machinery	to	 ensure	that	any	mutations	during	this	S-phase	are	quickly	and	accurately	repaired;	lack	of	 ability	to	repair	DNA	damage	can	allow	a	cell	to	mutate	into	something	new,	sometimes	 something	cancerous. Resveratrol	intercedes	in	S-phase	to	damage	newly-replicated	cell	DNA.	“The	healthy	cells	 can	repair	the	damage,	but	cancer	cells	can’t	and	when	we	treat	cancer	cells	with	resveratrol,	we	see	arrest	in	the	S-phase,”	says	Agarwal.	In	healthy	cells,	the	repair	is	instant	 and	makes	no	difference	to	the	newly-born	copy	whatsoever,	but	the	lack	of	repair	that	 allows	a	cell	to	become	cancerous	also	makes	it	fragile	–	to	most	cells	implicated	in	head	 and	neck	squamous	cell	carcinomas,	the	DNA	damage	of	resveratrol	during	S-phase	is	 fatal.	The	damaged	DNA	can’t	successfully	build	the	new	cell	and	the	spread	of	cancer	is	 stopped	cold. It’s	a	nifty	trick	that	exploits	a	fundamental	biological	difference	between	healthy	and		 cancerous	cells	to	kill	cancer	but	not	tissue	we’d	rather	keep. “The	population	we’d	like	to	focus	on	is	patients	who’ve	already	undergone	treatment		 for	head	and	neck	cancers	–	who	are	at	high	risk	for	recurrence	at	a	rate	of	about	50%,”	 says	Robert	Sclafani.	Specifically,	cancers	of	the	oral	cavity	are	a	likely	first	target	for	 resveratrol-based	treatments,	due	to	the	ease	of	drug	delivery	via	oral	mouthwash. Until	then:	“We	had	one	cell	line	that	was	so	sensitive	to	resveratrol	that	a	glass	of	red	 wine	would	probably	have	worked,”	says	Sclafani. But,	“You	can’t	just	drink	more	wine,”	says	Agarwal,	 who	points	out	that	consuming	the	level	of	resveratrol	 needed	to	kill	the	vast	majority	of	head	and	neck		 cancers	through	red	wine	is	simply	impractical.	But,	 while	more	research	is	needed,	Agarwal	muses	that	 perhaps	a	glass	of	wine	per	night	combined	with	the	 resveratrol	found	in	peanut-rich	Thai	food	could	be	a	 moderate	prophylactic	against	the	development	of	head	 and	neck	cancers.
Garth Sundem is a University of Colorado Cancer Center science writer Rajesh Agarwal, PhD

Drs. Joel Marrs and Sarah Anderson flank patient Morolene Rogers

Denver Health Eastside Adult Internal Medicine Clinic
Drs.	Sarah	Anderson	and	Joel	Marrs,	Assistant		 Professors	at	the	University	of	Colorado	School		 of	Pharmacy,	practice	clinically	at	the	Denver	 Health	Eastside	Adult	Internal	Medicine	Clinic		 in	Denver,	Colorado.		The	ambulatory	clinical		 practice	partnership	between	Denver	Health	and	 University	of	Colorado	has	been	in	existence	since	 2009.		Drs.	Anderson	and	Marrs	provide	direct		 patient	care	through	hypertension/resistant		 hypertension	clinic	and	anticoagulation	clinic.	 In	addition	to	these	in-person	patient	visits,	Drs.	 Anderson	and	Marrs	perform	telephonic	diabetes	 management	and	telephonic	hospital	discharge	 follow-up.		One	of	the	newest	ventures	within	the	 clinic	is	team	participation	by	the	University	of	 Colorado	School	of	Pharmacy	and	Denver	Health	 in	the	Health	Resources	and	Services	Administration	(HRSA)	Patient	Safety	and	Clinical	Pharmacy	 Services	Collaborative	(PSPC)	3.0.		Drs.	Anderson	 and	Marrs	are	working	within	their	clinic	and	with	 the	outpatient	pharmacy	to	target	patients	who	 have	uncontrolled	diabetes	(defined	as	an	A1C	>	9	 percent)	to	achieve	better	glycemic	control	through	 medication	titrations,	diabetes	education,	and	improvements	in	medication	adherence.	Through	their	 collaborative	involvement	in	managing	diabetic	 patients	at	the	clinic	there	is	now	55	more	diabetic	 patients	at	an	A1C	goal	of	less	than	7	percent	than	 prior	to	clinical	pharmacy	services	being	offered	at	 the	clinic.

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CU School of Pharmacy
Pharmacy Perspectives - Fall 2011

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