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Cytotoxicity and Multidrug -Resistance Reversing Activity of Extracts from Gamma-Irradiated Coix Zachryma-jobi L. var. ma-yuen Stapf Seed

감마선 조사된 율무종자의 세포독성 및 다제내성 극복활성

  • Cha, Young-Ju (Biology Research Center of industrial Accelerators, Dongshin University) ;
  • Lee, Sook-Young (Biology Research Center of industrial Accelerators, Dongshin University)
  • 차영주 (동신대학교 산업용가속기이용생물연구센터) ;
  • 이숙영 (동신대학교 산업용가속기이용생물연구센터)
  • Published : 2005.06.01

Abstract

This study was carried out to examine the effects of gamma irradiation on the cytotoxicity and multidrug-resistance reversing activity of methanol extracts from Coix lachryma-jobi L. var. me-yuen Stapf seed. The seed was irradiated with doses of 1, 4, 8, 16, 32 and 64 Gy of the gamma radiation, and then extracted by methanol. The extracts were examined for cytotoxicity on the human cancer cell lines, MCF-7 (human breast adenocarcinoma pleural effusion), Calu-6 (human pulmonary carcinoma) and SNU-601 (human gastric carcinoma) cells, and investigated for multidrug-resistance reversing activity using drug sensitive AML-2/WT and multidrug-resistant AML-2/D100 cells. The growth inhibitory activity of irradiated seed extracts on human cancer cell lines was higher than that of the control. In the case of Calu-6 cell line, the effect of cytotoxicity was observed in the extracts of 4, 8 and 16 Gy. $IC_{50}$ value in the MCF-7 cell line was measured in the only 8 Gy extract. And in the SNU-601 cell line as Calu-6, the effect of cytotoxicity was observed in the extracts of 4, 8 and 16 Gy. But the extracts of gamma-irradiated seed over 32 Gy showed little growth inhibitory effect against human cancer cell lines. In this result, 8 Gy extract had significant growth inhibitory in all human cancer cell lines $(Calu-6:\;633\;{\mu}g/mL,\;MCF-7:\;653\;{\mu}g/mL\;and\;SNU-601:\;683\;{\mu}g/mL)$. The extracts of 4, 8 and 16 Gy strongly potentiated vincristine cytotoxicity in AML-2/D100 cells. The reversal fold (RF) of 4, 8 and 16 Gy extracts was 1.7, 1.8 and 1.6, respectively. But their cytotoxicities to both sensitive AML-2/WT and resistant AML-2/D100 cells were in the same order of magnitude. These results indicate that the above samples would contain some principles which have cytotoxicity and multidrug-resistance reversing activity. Irradiation technology can be applied to promote physiological activities of medicinal plant seeds.

율무종자에 0, 1, 4, 8, 16, 32 및 64 Gy 선량의 감마선을 조사한 후 메탄을 추출하였으며 조사 종자 추출물이 인체의 유방암세포주(MCF-7), 폐암세포주(Calu-6), 위암세포주(SNU-601), 그리고 인체 급성골수성백혈암세포주(AML-2/WT)에 대한 세포독성 및 다제내성세포주(AML-2/D100)에 대한 다제내성 극복활성에 미치는 영향을 알아보고자 MTT 방법을 이용하여 분석하였다. 감마선 조사한 율무종자의 추출물은 대조구보다 비교적 낮은 농도에서 암세포 증식 저해 활성을 나타내는 경향을 보였으며 그 활성은 암세포 주와 조사선량별 추출물에 따라 다르게 나타났다. Calu-6의 경우 4, 8 및 16 Gy 추출물에서 암세포 증식 억제 효과를 나타냄을 알 수 있었으며 MCF-7에서 는 유일하게 8 Gy 추출물에서 $IC_{50}$값을 측정할 수 있었다. 그리고 SNU-601의 경우는 Calu-6에서와 같이 4, 8 및 16 Gy 추출물에서 증식저해 활성을 관찰할 수 있었으나 그 활성은 대조구인 0 Gy 추출물 보다 약간 높은 농도에서 관찰되었다. 한편, 선량이 높을수록 즉, 32 Gy 이상 감마선 조사는 암세포 증식억제 활성을 거의 나타내지 않았다. 유의할 만한 결과로는 8 Gy추출물이 3가지 암세포$(Calu-6:\;633\;{\mu}g/mL,\;MCF-7:\;653\;{\mu}g/mL,\;SNU-601:\;683\;{\mu}g/mL)$ 모두에서 증식 억제 활성을 나타냈다. 다제내성 세포에 대한 감수성 세포의 세포독성도를 측정하여 선택독성을 관찰한 결과 4,8 및 16 Gy추출물들은 오히려 감수성 세포에 대한 세포독성이 높게 나타나 교차내성을 나타내지 않았다. 그러나 다제내성 세포에 대하여 항암제인 vincristine과 함께 추출물을 처리한 결과 내성극복도(RF)가 4, 8 및 16 Gy 추출물에서 각각 1.7, 1.8 및 1.6으로서 다제내성 조절 활성을 관찰할 수 있었다. 따라서 감마선 조사기술은 약용식물 종자의 생리활성 증진에 활용 가능성이 매우 높을 것으로 기대된다.

Keywords

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