Differences in the rates of protein degradation in untransformed and transformed cell lines

Otsuka, Hidenori; Moskowitz, Merwin

doi:10.1016/0014-4827(78)90533-5

Cited by 33 publications

(19 citation statements)

References 16 publications

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“…9,[13][14][15] Furthermore, cancer cells show less autophagy than normal cells. 16,17) These findings indicate that autophagy induction is an attractive modality of anticancer therapy.…”

Section: )mentioning

confidence: 97%

“…9,[13][14][15] Furthermore, cancer cells show less autophagy than normal cells. 16,17) These findings indicate that autophagy induction is an attractive modality of anticancer therapy.b-Carboline alkaloids occur in a number of medicinal plants such as Peganum harmala, Passiflora edulis, Passiflora incarnata, and Banisteriopsis caapi.18,19) These plants have been used in traditional medicine to treat asthma, jaundice, lumbago, and other human ailments.19-21) Recently, it has been reported that certain b-carboline alkaloids and their related compounds have cytotoxic effects on cancer cells. [22][23][24] We also reported previously that harmol, a b-carboline alkaloid, induces caspase-8-dependent and Fas/Fas ligand-independent apoptosis in human NSCLC H596 cells (adenosquamous carcinoma).…”

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confidence: 99%

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The .BETA.-Carboline Alkaloid Harmol Induces Cell Death via Autophagy but Not Apoptosis in Human Non-small Cell Lung Cancer A549 Cells

Abe

Yamada

Moriya

et al. 2011

Biological & Pharmaceutical Bulletin

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Lung cancer is a leading cause of death worldwide, and the long-term survival rate of lung cancer patients is one of the lowest among cancers.1,2) Two major types of lung cancer have been identified: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC, the most prevalent subtype, is relatively resistant to chemotherapy and radiation therapy. On the other hand, SCLC is initially highly sensitive to chemotherapy and radiation therapy, but shows resistance to treatment in the majority of patients.3) The high mortality in NSCLC is due to the difficulty of early diagnosis and its high potential for local invasion and distant metastasis. Although relatively effective chemotherapeutic agents have been developed, lung cancer still has a low cure rate. Furthermore, the adverse effects of chemotherapeutic compounds often hamper the quality of life of lung cancer patients. Therefore, the discovery of effective novel prophylactic, diagnostic, and therapeutic treatments for NSCLC is urgently needed."Apoptosis" has been used as a synonym for programmed cell death (PCD), and is a well-known form of PCD. Since the 1960s, various morphological forms of PCD have been recognized. Clarke classified cell death into 4 types, including type I PCD (apoptosis) and type II PCD (autophagy). 4)Numerous studies have demonstrated that most chemotherapy agents and certain naturally occurring compounds induce cell death by activating the apoptotic pathway. It is thought that apoptosis induction in tumor cells with either drugs or natural products is effective therapy for cancer and immune system diseases. On the other hand, autophagy is one of the major regulatory mechanisms in the degradation of intracellular proteins and organelles. 5,6) During autophagy, the cytosol and whole organelles become encased in double-membrane vacuoles such as autophagosomes, and subsequently fuse with lysosomes.5) Degradation of the sequestered material generates nucleotides, amino acids, and free fatty acids that are recycled for macromolecular synthesis and ATP generation.7) Although originally characterized as a survival response to nutrient deficiency, autophagy is now recognized as frequently induced in response to a variety of stressors to maintain cellular homeostasis. [8][9][10][11][12] In recent years, the importance of autophagy has been emphasized in various biological fields, including cancer. 9,[13][14][15] Furthermore, cancer cells show less autophagy than normal cells. 16,17) These findings indicate that autophagy induction is an attractive modality of anticancer therapy.b-Carboline alkaloids occur in a number of medicinal plants such as Peganum harmala, Passiflora edulis, Passiflora incarnata, and Banisteriopsis caapi.18,19) These plants have been used in traditional medicine to treat asthma, jaundice, lumbago, and other human ailments.19-21) Recently, it has been reported that certain b-carboline alkaloids and their related compounds have cytotoxic effects on cancer cells. [22][23][24] We also reported previously that harm...

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“…9,[13][14][15] Furthermore, cancer cells show less autophagy than normal cells. 16,17) These findings indicate that autophagy induction is an attractive modality of anticancer therapy.…”

Section: )mentioning

confidence: 97%

mentioning

confidence: 99%

The .BETA.-Carboline Alkaloid Harmol Induces Cell Death via Autophagy but Not Apoptosis in Human Non-small Cell Lung Cancer A549 Cells

Abe

Yamada

Moriya

et al. 2011

Biological & Pharmaceutical Bulletin

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“…It is widely believed that there is a link between carcinogenesis and decreased levels of basal autophagy. 22,23 The tumour-suppressor beclin 1 (BECN1), a mammalian homologue of yeast Atg6/Vps30, which is essential for the induction of autophagy in response to nitrogen deprivation, is mono-allelically deleted in 40-75% of human sporadic breast, prostate and ovarian cancers. 24 Introduction of BECN1 into MCF-7 cells induced autophagy and inhibited cell proliferation, in vitro clonogenicity and tumourigenicity.…”

Section: Imatinib and Cellular Autophagymentioning

confidence: 99%

The anticancer drug imatinib induces cellular autophagy

et al. 2007

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The tyrosine kinase inhibitor imatinib (Gleevec, Novartis Pharmaceuticals Corporation; Basel, Switzerland) is a powerful drug for treatment of chronic myelogenous leukemia (CML) and other malignancies. It selectively targets various tyrosine kinases, thereby leading to growth arrest of respective cancer cells. Given its wide application, it is of high importance to know all related underlying molecular mechanisms. We had previously found that imatinib increases the cellular clearance of intracellular protein aggregates by targeting the abl pathway and thereby upregulating lysosomal activity. Here, we describe that imatinib dose dependently activates the cellular autophagy machinery in mammalian cells, independently of tissue type, species origin or immortalization status of cells. Autophagy is an archetypical cellular degradation mechanism implicated in many physiological and pathophysiological conditions. Our data link for the first time the process of autophagy with the mode of action of imatinib. Induction of autophagy might represent an additional mechanism of imatinib to induce growth arrest, promote apoptosis in cancer cells and eventually even promote tumour regression. Leukemia (2007) 21, 936-942.

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“…Moreover, there is often an inverse relationship between autophagic activity and malignant potential, raising the possibility that defects in cellular autophagy contribute to the development of cancer. Specifically, malignant or transformed cells often display lower basal autophagic activity than their normal counterparts and do not show increased autophagic protein degradation rates in response to serum deprivation or high cell density (10)(11)(12)(13). In rat liver carcinogenesis models, autophagic activity is mildly reduced at a preneoplastic stage and becomes more substantially diminished in primary hepatocellular tumor cells (14).…”

Section: Introductionmentioning

confidence: 99%

Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene

et al. 2003

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Malignant cells often display defects in autophagy, an evolutionarily conserved pathway for degrading long-lived proteins and cytoplasmic organelles. However, as yet, there is no genetic evidence for a role of autophagy genes in tumor suppression. The beclin 1 autophagy gene is monoallelically deleted in 40-75% of cases of human sporadic breast, ovarian, and prostate cancer. Therefore, we used a targeted mutant mouse model to test the hypothesis that monoallelic deletion of beclin 1 promotes tumorigenesis. Here we show that heterozygous disruption of beclin 1 increases the frequency of spontaneous malignancies and accelerates the development of hepatitis B virus-induced premalignant lesions. Molecular analyses of tumors in beclin 1 heterozygous mice show that the remaining wildtype allele is neither mutated nor silenced. Furthermore, beclin 1 heterozygous disruption results in increased cellular proliferation and reduced autophagy in vivo. These findings demonstrate that beclin 1 is a haplo-insufficient tumor-suppressor gene and provide genetic evidence that autophagy is a novel mechanism of cell-growth control and tumor suppression. Thus, mutation of beclin 1 or other autophagy genes may contribute to the pathogenesis of human cancers.This article was published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org.

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Differences in the rates of protein degradation in untransformed and transformed cell lines

Cited by 33 publications

References 16 publications

The .BETA.-Carboline Alkaloid Harmol Induces Cell Death via Autophagy but Not Apoptosis in Human Non-small Cell Lung Cancer A549 Cells

The .BETA.-Carboline Alkaloid Harmol Induces Cell Death via Autophagy but Not Apoptosis in Human Non-small Cell Lung Cancer A549 Cells

The anticancer drug imatinib induces cellular autophagy

Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene

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