• BMB Reports
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• 제54권11호
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• pp.575-580
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• 2021

Cisplatin is widely known as an anti-cancer drug. However, the effects of cisplatin on mitochondrial function and autophagy-related proteins levels in the skeletal muscle are unclear. The purpose of this study was to investigate the effect of different doses of cisplatin on mitochondrial function and autophagy-related protein levels in the skeletal muscle of rats. Eight-week-old male Wistar rats (n = 24) were assigned to one of three groups; the first group was administered a saline placebo (CON, n = 10), and the second and third groups were given 0.1 mg/kg body weight (BW) (n = 6), and 0.5 mg/kg BW (n = 8) of cisplatin, respectively. The group that had been administered 0.5 mg cisplatin exhibited a reduced BW, skeletal muscle tissue weight, and mitochondrial function and upregulated levels of autophagy-related proteins, including LC3II, Beclin 1, and BNIP3. Moreover, this group had a high LC3 II/I ratio in the skeletal muscle; i.e., the administration of a high dose of cisplatin decreased the muscle mass and mitochondrial function and increased the levels of autophagy-related proteins. These results, thus, suggest that reducing mitochondrial dysfunction and autophagy pathways may be important for preventing skeletal muscle atrophy following cisplatin administration.

• Tuberculosis and Respiratory Diseases
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• 제69권2호
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• pp.81-94
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• 2010

Background: Autophagy is an important adaptive mechanism in normal development and in response to changing environmental stimuli in cancer. Previous papers have reported that different types of cancer underwent autophagy to obtain amino acids as energy source of dying cells in nutrient-deprived conditions. However, whether or not autophagy in the process of lung cancer causes death or survival is controversial. Therefore in this study, we investigated whether nutrient deprivation induces autophagy in human H460 lung cancer cells. Methods: H460, lung cancer cells were incubated in RPMI 1640 medium, and the starved media, which are BME and RPMI media without serum, including 2-deoxyl-D-glucose according to time dependence. To evaluate the viability and find out the mechanism of cell death under nutrient-deprived conditions, the MTT assay and flow cytometry were done and analyzed the apoptotic and autophagic related proteins. It is also measured the development of acidic vascular organelles by acridine orange. Results: The nutrient-deprived cancer cell is relatively sensitive to cell death rather than normal nutrition. Massive cytoplasmic vacuolization was seen under nutrient-deprived conditions. Autophagic vacuoles were visible at approximately 12 h and as time ran out, vacuoles became larger and denser with the increasing number of vacuoles. In addition, the proportion of acridine orange stain-positive cells increased according to time dependence. Localization of GFP-LC3 in cytoplasm and expression of LC-3II and Beclin 1 were increased according to time dependence on nutrient-deprived cells. Conclusion: Nutrient deprivation induces cell death through autophagy in H460 lung cancer cells.

• 생명과학회지
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• 제32권4호
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• pp.310-317
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• 2022

최근 인체에 유해한 요인으로 대기오염의 주성분인 미세먼지에 대한 관심이 증가하고 있다. 특히 직경이 2.5 ㎛ 미만인 PM_2.5는 인간의 폐 상피세포에서 자가포식을 동반한 산화적 스트레스를 유발하는 것으로 알려져 있다. 그러나 PM_2.5가 산화적 스트레스 하에서 자가포식을 증가시키는지와 이 과정이 ROS 의존적인지에 대한 연구는 충분하지 않은 실정이다. 본 연구에서는 PM_2.5가 인간 폐 상피 A594 세포에서 ROS 생성을 통해 자가포식을 촉진하는지를 조사하였다. 우리의 결과에 의하면, PM_2.5와 H₂O₂를 함께 처리한 세포에서는 각각이 단독 처리된 세포에 비하여 세포 생존력이 유의적으로 감소하였으며, 이는 전체 및 미토콘드리아 ROS 생성의 증가와 관련이 있었다. 또한, PM_2.5와 H₂O₂의 동시 처리는 Cyto-ID 염색을 통해 확인된 바와 같이 자가포식 유도의 증가와 LC3, p62 및 beclin 1과 같은 자가포식 바이오 마커 단백질의 발현을 증가시켰다. 그러나 NAC의 전처리에 의하여 ROS의 생성을 인위적으로 차단하였을 경우, PM_2.5와 H₂O₂의 동시 처리에 의한 세포 생존율의 감소와 자가포식 유도는 현저하게 억제되었다. 따라서, PM_2.5에 의해 유도된 ROS 생성이 A549 세포에서 자가포식 유도에 중요한 역할을 할 것으로 추측되며, 이는 PM_2.5에 의해 유도될 수 있는 폐 기능 손상이 산화적 스트레스 하에서 더욱 증가할 수 있음을 의미한다.