Analysis of cellular sensitization with cisplatin-induced apoptosis by glucose-starved stress in cisplatin-sensitive and resistant A431 cell line

H. Mese, Akira Sasaki, S. Nakayama, S. Yokoyama, S. Sawada, T. Ishikawa, T. Matsumura

Research output: Contribution to journalArticle

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Abstract

Background: Most solid tumors show resistance to current chemotherapy. This drug resistance can be associated with stress conditions, such as glucose starvation, low pH and hypoxia. These conditions are not observed in normal tissues. These tumor specific conditions commonly cause the glucose-regulated stress response of cancer cells. This stress response leads to induction of resistance to multiple anticancer drugs, such as etoposide, doxorubicin, camptothecin and vincristine. An examination was made of the effect of the glucose-regulated protein (GRP)-inducing conditions on cellular sensitivity to cisplatin (CDDP), which is a widely used drug against solid tumors. Materials and Methods: We used CDDP resistant subline A431/CDDP2 from human epidermoid carcinoma cell line A431 as previously established. Glucose-starved response showed GRP78 protein by Western blotting. We generated the glucose-starved condition by exposing cells to 2-deoxyglucose (2-DG) and examined cellular sensitivity to CDDP. We next examined CDDP induced apoptosis in glucose-starved condition. Furthermore, we determined the JNK1/SAPK and caspase-3 protein levels by Western blotting. Results: The glucose- starved condition was up-regulate GRP78 in the parent A431 cell (A431/P). On the other hand, in A431/CDDP2, GRP78 levels were not changed. The GRP78 inducing stress condition led to cellular sensitization to CDDP in A431/P cells only. DNA fragmentation of A431/P treated with 2-DG increased CDDP-induced apoptosis. A431/CDDP2 was not different with CDDP induced apoptosis in glucose-starved stress condition. The reduction of CDDP-induced apoptosis under glucose-starved stress condition was influenced by JNK1/SAPK and caspase-3 proteins. Conclusion: These results indicated that the glucose-starved stress condition was associated with increased sensitivity to CDDP in the up-regulated GRP78 cells. Furthermore, the reduction of CDDP- induced apoptosis can be considered as one of the CDDP resistant mechanisms in a glucose- starvation condition.

Original languageEnglish
Pages (from-to)1029-2034
Number of pages1006
JournalAnticancer Research
Volume21
Issue number2 A
Publication statusPublished - 2001

Fingerprint

Cisplatin
Apoptosis
Glucose
Cell Line
Deoxyglucose
Starvation
Caspase 3
Neoplasms
Western Blotting
Camptothecin
Proteins
Vincristine
DNA Fragmentation
Etoposide
Drug Resistance
Pharmaceutical Preparations
Doxorubicin
Squamous Cell Carcinoma
Up-Regulation
Drug Therapy

Keywords

  • Apoptosis
  • Caspase-3
  • CDDP resistance
  • Glucose-starved stress
  • GRP78
  • JNK1/SAPK

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Analysis of cellular sensitization with cisplatin-induced apoptosis by glucose-starved stress in cisplatin-sensitive and resistant A431 cell line. / Mese, H.; Sasaki, Akira; Nakayama, S.; Yokoyama, S.; Sawada, S.; Ishikawa, T.; Matsumura, T.

In: Anticancer Research, Vol. 21, No. 2 A, 2001, p. 1029-2034.

Research output: Contribution to journalArticle

Mese, H, Sasaki, A, Nakayama, S, Yokoyama, S, Sawada, S, Ishikawa, T & Matsumura, T 2001, 'Analysis of cellular sensitization with cisplatin-induced apoptosis by glucose-starved stress in cisplatin-sensitive and resistant A431 cell line', Anticancer Research, vol. 21, no. 2 A, pp. 1029-2034.
Mese, H. ; Sasaki, Akira ; Nakayama, S. ; Yokoyama, S. ; Sawada, S. ; Ishikawa, T. ; Matsumura, T. / Analysis of cellular sensitization with cisplatin-induced apoptosis by glucose-starved stress in cisplatin-sensitive and resistant A431 cell line. In: Anticancer Research. 2001 ; Vol. 21, No. 2 A. pp. 1029-2034.
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T1 - Analysis of cellular sensitization with cisplatin-induced apoptosis by glucose-starved stress in cisplatin-sensitive and resistant A431 cell line

AU - Mese, H.

AU - Sasaki, Akira

AU - Nakayama, S.

AU - Yokoyama, S.

AU - Sawada, S.

AU - Ishikawa, T.

AU - Matsumura, T.

PY - 2001

Y1 - 2001

N2 - Background: Most solid tumors show resistance to current chemotherapy. This drug resistance can be associated with stress conditions, such as glucose starvation, low pH and hypoxia. These conditions are not observed in normal tissues. These tumor specific conditions commonly cause the glucose-regulated stress response of cancer cells. This stress response leads to induction of resistance to multiple anticancer drugs, such as etoposide, doxorubicin, camptothecin and vincristine. An examination was made of the effect of the glucose-regulated protein (GRP)-inducing conditions on cellular sensitivity to cisplatin (CDDP), which is a widely used drug against solid tumors. Materials and Methods: We used CDDP resistant subline A431/CDDP2 from human epidermoid carcinoma cell line A431 as previously established. Glucose-starved response showed GRP78 protein by Western blotting. We generated the glucose-starved condition by exposing cells to 2-deoxyglucose (2-DG) and examined cellular sensitivity to CDDP. We next examined CDDP induced apoptosis in glucose-starved condition. Furthermore, we determined the JNK1/SAPK and caspase-3 protein levels by Western blotting. Results: The glucose- starved condition was up-regulate GRP78 in the parent A431 cell (A431/P). On the other hand, in A431/CDDP2, GRP78 levels were not changed. The GRP78 inducing stress condition led to cellular sensitization to CDDP in A431/P cells only. DNA fragmentation of A431/P treated with 2-DG increased CDDP-induced apoptosis. A431/CDDP2 was not different with CDDP induced apoptosis in glucose-starved stress condition. The reduction of CDDP-induced apoptosis under glucose-starved stress condition was influenced by JNK1/SAPK and caspase-3 proteins. Conclusion: These results indicated that the glucose-starved stress condition was associated with increased sensitivity to CDDP in the up-regulated GRP78 cells. Furthermore, the reduction of CDDP- induced apoptosis can be considered as one of the CDDP resistant mechanisms in a glucose- starvation condition.

AB - Background: Most solid tumors show resistance to current chemotherapy. This drug resistance can be associated with stress conditions, such as glucose starvation, low pH and hypoxia. These conditions are not observed in normal tissues. These tumor specific conditions commonly cause the glucose-regulated stress response of cancer cells. This stress response leads to induction of resistance to multiple anticancer drugs, such as etoposide, doxorubicin, camptothecin and vincristine. An examination was made of the effect of the glucose-regulated protein (GRP)-inducing conditions on cellular sensitivity to cisplatin (CDDP), which is a widely used drug against solid tumors. Materials and Methods: We used CDDP resistant subline A431/CDDP2 from human epidermoid carcinoma cell line A431 as previously established. Glucose-starved response showed GRP78 protein by Western blotting. We generated the glucose-starved condition by exposing cells to 2-deoxyglucose (2-DG) and examined cellular sensitivity to CDDP. We next examined CDDP induced apoptosis in glucose-starved condition. Furthermore, we determined the JNK1/SAPK and caspase-3 protein levels by Western blotting. Results: The glucose- starved condition was up-regulate GRP78 in the parent A431 cell (A431/P). On the other hand, in A431/CDDP2, GRP78 levels were not changed. The GRP78 inducing stress condition led to cellular sensitization to CDDP in A431/P cells only. DNA fragmentation of A431/P treated with 2-DG increased CDDP-induced apoptosis. A431/CDDP2 was not different with CDDP induced apoptosis in glucose-starved stress condition. The reduction of CDDP-induced apoptosis under glucose-starved stress condition was influenced by JNK1/SAPK and caspase-3 proteins. Conclusion: These results indicated that the glucose-starved stress condition was associated with increased sensitivity to CDDP in the up-regulated GRP78 cells. Furthermore, the reduction of CDDP- induced apoptosis can be considered as one of the CDDP resistant mechanisms in a glucose- starvation condition.

KW - Apoptosis

KW - Caspase-3

KW - CDDP resistance

KW - Glucose-starved stress

KW - GRP78

KW - JNK1/SAPK

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