Dichloromethane fraction from Gardenia jasminoides: DNA topoisomerase 1 inhibition and oral cancer cell death induction.
BACKGROUND
A growing body of evidence shows that compounds of plant origin have the ability to prevent cancer. The fruit of gardenia, Gardenia jasminoides Ellis (Rubiaceae), has long been used as a food additive and herbal medicine, and its pharmacological actions, such as protective activity against oxidative damage, cytotoxic effect, and anti-inflammatory and anti-tumor activity, have already been reported.


OBJECTIVE
The purpose of the present study was to investigate the presence of DNA topoisomerase 1 inhibitor in various solvent fractions of Gardenia extract and examine the induction of oral cancer cell death upon treatment with Gardenia extract.


METHODS
The methanol extract of Gardenia was partitioned with n-hexane, dichloromethane, ethyl acetate, n-butanol, and water.


RESULTS
In the DNA topoisomerase 1 assay, n-hexane and dichloromethane fractions inhibited topoisomerase 1 and led to a decrease in the cell viability of KB cells. The dichloromethane fraction (0.1 mg/mL) also showed 77% inhibition of cell viability in KB cells compared with HaCaT cells. Treatment with dichloromethane fraction led to apoptotic cell death as evidenced by flow cytometric analysis and morphological changes. In addition, treatment with Gardenia extract dichloromethane fraction led to the partial increase of caspase-3, caspase-8 and caspase-9 activities and the cleavage of poly (ADP-ribose) polymerase.


CONCLUSIONS
Taken together, these results suggest that the dichloromethane fraction from Gardenia extract induces apoptotic cell death by DNA topoisomerase 1 inhibition in KB cells. These findings suggest the possibility that Gardenia extract could be developed as an anticancer modality.
Lim
WonBong
W
Second Stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea.
Kim
OkSu
O
Jung
JinAn
J
Ko
YoungJong
Y
Ha
JooWon
J
Oh
HeeKyun
H
Lim
HoiSoon
H
Kwon
Hyukil
H
Kim
InAe
I
Kim
Jisun
J
Kim
MiSook
M
Kim
SeoYune
S
Kim
Byung-kuk
BK
Kim
SunMi
S
Kang
Byung-Cheol
BC
Choi
HongRan
H
Kim
OkJoon
O
D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000187:drug effects; D005434:Flow Cytometry; D005638:Fruit; D032062:Gardenia / Q000737:chemistry*; D006801:Humans; D007624:KB Cells; D008752:Methylene Chloride / Q000737:chemistry; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D012997:Solvents / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D012997:Solvents; D008752:Methylene Chloride; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D004264:DNA Topoisomerases, Type I