The ethyl acetate fraction of Gynura procumbens sensitizes widr colon cancer cell line against 5-fluorouracil but shows antagonism with cisplatin

Authors

  • Nunuk Aries Nurulita Graduate Program of Pharmaceutical Science, Faculty of Pharmacy, Gadjah Mada University, Sekip Utara Jogjakarta, Indonesia
  • Edy Meiyanto Cancer Chemoprevention Research Center, Faculty of Pharmacy, Gadjah Mada University, sekip Utara II, Yogyakarta 55281, Indonesia
  • Sugiyanto Departement of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Gadjah Mada University, Sekip Utara, Yogyakarta 55281, Indonesia
  • Eishou Matsuda Laboratorium of Gene Function of Animal, Nara Institute of Science and Technology, Takayama, Ikoma, Japan.
  • Masashi Kawaichi Laboratorium of Gene Function of Animal, Nara Institute of Science and Technology, Takayama, Ikoma, Japan

Keywords:

Gynura procumbens, WiDr, G1 and S phase arrest, apoptosis

Abstract

Our recent study has evaluated the ethyl acetate fraction of Gynura procumbens (FEG) as co-chemotherapeutic agent in combination with 5- fluorouracil (5-FU) and cisplatin (CISP) against WiDr colon cancer cells. This study aimed to assess whether FEG produced synergistic effect with 5- FU and CISP and to evaluate its regulation on proliferation, cell cycle, and cell death induction on WiDr colon cancer cells. (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay was performed to determine the growth inhibitory effect of both single (FEG, 5-FU, or CISP) and combination treatments. FEG (25-500 μg/mL), 5- FU (25-1000 μM) and CISP (5-100 μM) inhibited cells growth in a dose dependent manner and exhibited an IC50 value of 125 μg/mL, 848 M and 43 M, respectively. FEG sensitized WiDr cells that was treated by 5-FU, boosting its therapeutic potential. Conversely when FEG was combined with CISP, it caused antagonism. The antiproliferative effect of single and combination treatment was determined by studying the cell proliferation kinetics using MTT assay. Flowcytometry and (4’,6-diamidino-2- phenylindole) DAPI staining was used to disclose the mechanism of cell cycle arrest and apoptosis. FEG inhibited cell proliferation, induced G1 and S phase arrest and apoptosis. The inhibitory effect was enhanced when FEG was combined with 5-FU, differing from CISP. According to the datas obtained, FEG possess sensitizing properties causes cell cycle arrest and cell death suppose to be apoptosis on WiDr cells. FEG demonstrates a possibility of additive to synergism properties when combined with 5-FU but shows antagonis with CISP.

References

. Perry LM. Medicinal plants of east and

southeast Asia: attributed properties and

uses, The MIT press, USA; 1980. p.94.

. Iskander MN, Song Y, Coupar IM,

Jiratchariyakul W. Antiinflamatory

screening of medicinal plant G.

Procumbens. Plant Foods Hum Nutr.

; 57: 233-244.

. Kim M, Lee HJ, Wiryowidagdo S, Kim

HK. Antihypertensive effects of G.

Procumbens extract in spontaneously

hypertensive Rats. J Med Food. 2006;

(4): 587-590.

. Rosidah YMF, Sadikun A, Asmawi MZ.

Antioxidant potential of Gynura

procumbens. Pharmaceutical Biol. 2008;

: 616-625.

. Sugiyanto, Sudarto, Meiyanto E, Nugroho

AE, Jenie UA. The anticarcinogenic

activity of plants compounds. Indonesian

Journal of Pharmacy. 2003; 14(4): 216-

. Meiyanto E, Susilowati S, Tasminatun S,

Murwanti R, Sugiyanto.

Chemopreventive effect of ethanolic

extract of Gynura procumbens (Lour),

Merr on the carcinogenesis of Rat breast

cancer development, Indonesian Journal

of Pharmacy. 2007; 18(3): 154-161.

. Meiyanto E, Septisetyani EP.

Antiproliferative and apoptotic effect of

fenolic fraction of ethanolic extract of

Gynura procumbens (Lour.) Merr. against

HeLa Cells. Artocarpus. 2005; 5(2): 74-

. Jenie RI, Meiyanto E, Murwanti R.

Antiangiogenic effect of sambung nyawa

leaves (Gynura procumbens (Lour.)

Merr.) etanolic extract on chick embryo

chorioallantoic membrane (CAM).

Indonesian Journal of Pharmacy. 2006;

(1): 50-55.

. Jenie RI, Meiyanto E. Co-chemotherapy

of sambung nyawa (Gynura procumbens

(Lour.) Merr.) leaves ethanolic extract and

Doxorubicin on breast cancer cell.

Indonesian Journal of Pharmacy. 2007;

(2): 81-87.

. Lee HJ, Lee BC, Chung JH,

Wiryowidagdo S, Chun W, Kim SS, Kim

H, Choe M. Inhibitory effects of aqueous

extract of Gynura procumbens on human

mesangial cell proliferation. Korean J

Physiol Pharmacol. 2007; 11: 145-148.

. Sadikun A, Idus A, Ismail N., Sterol and

sterol glycosides from the leaves of

Gynura procumbens. Nat Prod Sci. 1996;

-23.

. American Cancer Society (ACS). Cancer

Facts & Figures 2009, Atlanta: American

Cancer Society. 2009. p. 1-3.

. Davis JM, Navolanic PM, WeinsteinOppenheimer CR, Steelman LS, Wei H,

Konopleva M, Blagosklonny MV,

McCubrey JA. Raf-1 and Bcl-2 Induce

Distinct and Common Pathways That

Contribute to Breast Cancer Drug

Resistance, ClinicalCancer Research.

; 9: 1161-1170.

. Notarbartolo M, Poma P, Perri D,

Dusonchet L, Cervello M, Alessandro N.

Antitumor effects of curcumin, alone or in

combination with cisplatin or

doxorubicin, on human hepatic cancer

cells. Analysis of their possible

relationship to changes in NF-кB

activation levels and in IAP gene

expression. Cancer Letter. 2005; 224: 53-

. Cardenas EE, Sanfridson A, Culter NS,

Heitmam J. Signal-transduction cas cades

as Target for Therapeutical Intervetion by

Natural Products. Tibtech. 1998; 16: 425-

. Violette S, Poulain L, Dussaulx E, Pepin

D, Faussat AM, Chambaz J, Lacorte JM,

Staedel C, Lesuffleur T. Resistance of

colon cancer cells to long-term 5-

fluorouracil exposure is correlated to the

relative level of BCl-2 and BCl-XL in

addition to Bax and p53 status. Int J

Cancer. 2002; 98: 498-504.

. Maryati, Meiyanto E, Riyanto S. Uji

Sitotoksik dan isolasi flavonoid dari fraksi

etil asetat daun Gynura procumbens

(Lour) Merr. Pharmacon. 2005; 6(2): 46-

. Huang WW, Chiu YJ, Fan MJ, Lu HF,

Yeh HF, Li KH, Chen PY, Chung JG,

Yang JS., Kaempferol induced apoptosis

via endoplasmic reticulum stress and

mitocondria-dependent pathway in human

osteosarcoma U-2 OS cells. Mol Nutr

Food Res. 2010; 54: 1-11.

. Choi EJ, Ahn WS. Kaempferol induced

the apoptosis via cell cycle arrest in

human breast cancer MDA-MB-453 cells.

Nutr Res Prac. 20082(4), 322-325.

. Priego S, Feddi F, Ferrer P, Mena S,

Benlloch M, Ortega A, Carretero J,

Obrador E, Miguel AM, Estrela JM.

Natural polyphenols facilitate elimination

of HT-29 colorectal cancer xenografts by

chemoradiotherapy: a Bcl-2- and

superoxide dismutase 2-dependent

mechanism. Mol Cancer Ther. 2008;

(10): 3330–42.

Downloads

Published

30-09-2011

How to Cite

1.
Nunuk Aries Nurulita, Edy Meiyanto, Sugiyanto, Eishou Matsuda, Masashi Kawaichi. The ethyl acetate fraction of Gynura procumbens sensitizes widr colon cancer cell line against 5-fluorouracil but shows antagonism with cisplatin. ijp [Internet]. 2011 Sep. 30 [cited 2024 Nov. 23];3(3):392-405. Available from: https://ijp.arjournals.org/index.php/ijp/article/view/120

Issue

Section

Original Research Articles