Autophagy is an important event for low-dose cytarabine treatment in acute myeloid leukemia cells

Chen, Liyun; Guo, Peng; Zhang, Yunxiang; Li, Xiaoyang; Jia, Pei-Min; Tong, Jianhua; Li, Junmin

doi:10.1016/j.leukres.2017.06.007

Cited by 27 publications

(25 citation statements)

References 22 publications

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“…Whether THC treatment can not only induce autophagy flux but also induce AML cell differentiation similar to ATRA treatment is worth investigating in the future. Ara‐C, an important agent in leukemia treatment, induces apoptosis and autophagy in leukemia cells (Chen et al, ; de Vries, Falkenburg, Willemze, & Barge, ). Dysregulation of the apoptosis and autophagy mechanisms leads to neoplasia formation and subsequent resistance to chemotherapy (Pan, Li, He, Qiu, & Zhou, ).…”

Section: Resultsmentioning

confidence: 99%

Curcumin and tetrahydrocurcumin induce cell death in Ara‐C‐resistant acute myeloid leukemia

Tseng

Chiou

Weng

et al. 2019

Phytotherapy Research

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Most anticancer agents induce cancer cell death; however, multidrug-resistant cancers often lead to treatment failure. The effective use of curcumin as an anticancer agent has been demonstrated in clinical trials. Tetrahydrocurcumin, a major curcumin metabolite, exhibits pharmacological activities similar to those of curcumin. Curcumin induces cell death mainly through the apoptosis pathway, and tetrahydrocurcumin induces cell death mainly via an autophagy pathway in HL60 cells. Here, we investigated whether curcumin and tetrahydrocurcumin can induce apoptosis-and autophagy-mediated cell deaths in Ara-C-resistant cancer cells, respectively. The results demonstrated that curcumin and tetrahydrocurcumin induced cell death by apoptosis and autophagy, respectively, in Ara-C-resistant HL60 cells. Thus, curcumin and tetrahydrocurcumin have potential applications in the treatment of acute myeloid leukemia with Ara-C resistance.

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Section: Resultsmentioning

confidence: 99%

Curcumin and tetrahydrocurcumin induce cell death in Ara‐C‐resistant acute myeloid leukemia

Tseng

Chiou

Weng

et al. 2019

Phytotherapy Research

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“…Autophagy was shown to contribute to both cytarabine and idarubicin's efficacy in AML cells. 39,40 Autophagy is also required for mitoxantrone-induced immunogenic signaling in tumors. 41 Moreover, arsenic trioxide, 42,43 vitamin D3, 44 vitamin K2, 45 eupalinin A (sesquiterpene lactone), 46 BAY11-7082 (NF-kB inhibitor), 47 morphinone (a morphin derivative), 48 APO866 (NAD biosynthesis inhibitor), 49 and platonin 50 have all been reported to induce leukemia cell death via activation of autophagy.…”

Section: Discussionmentioning

confidence: 99%

Caspase-3 controls AML1-ETO–driven leukemogenesis via autophagy modulation in a ULK1-dependent manner

Man

Tan

Sun

et al. 2017

Blood

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Key Points• Loss of Caspase-3 delays leukemogenesis in a mouse model for t(8;21) AML.• Loss of Caspase-3 triggers upregulation of ULK1 and induction of autophagy in leukemia-initiating cells.AML1-ETO (AE), a fusion oncoprotein generated by t(8;21), can trigger acute myeloid leukemia (AML) in collaboration with mutations including c-Kit, ASXL1/2, FLT3, N-RAS, and K-RAS. Caspase-3, a key executor among its family, plays multiple roles in cellular processes, including hematopoietic development and leukemia progression. Caspase-3 was revealed to directly cleave AE in vitro, suggesting that AE may accumulate in a Caspase-3-compromised background and thereby accelerate leukemogenesis. Therefore, we developed a Caspase-3 knockout genetic mouse model of AML and found that loss of Caspase-3 actually delayed AML1-ETO9a (AE9a)-driven leukemogenesis, indicating that Caspase-3 may play distinct roles in the initiation and/or progression of AML. We report here that loss of Caspase-3 triggers a conserved, adaptive mechanism, namely autophagy (or macroautophagy), which acts to limit AE9a-driven leukemia. Furthermore, we identify ULK1 as a novel substrate of Caspase-3 and show that upregulation of ULK1 drives autophagy initiation in leukemia cells and that inhibition of ULK1 can rescue the phenotype induced by Caspase-3 deletion in vitro and in vivo. Collectively, these data highlight Caspase-3 as an important regulator of autophagy in AML and demonstrate that the balance and selectivity between its substrates can dictate the pace of disease. (Blood. 2017;129(20):2782-2792

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“…In acute myeloid leukemia therapy, cytarabine is also used as one of the important drugs. Treatment with cytarabine has been shown to inhibit cell growth and to induce apoptosis via regulation of autophagy pathway in human leukemia cell lines (99).…”

Section: The Clinical Trials and Therapeutic Effects Of Cytarabine Andmentioning

confidence: 99%

Therapeutic Application of Diverse Marine-derived Natural Products in Cancer Therapy

Yun

Kim

2019

Anticancer Res

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Natural products (NPs) are useful sources of bioactive compounds and play important roles in the development and discovery of new drugs for diverse human diseases. Most natural products originate from terrestrial species, but diverse marine organisms are another source of new agents for cancer therapy. Natural products derived from marine organisms show diverse pharmacological activities via bioactive secondary metabolites. They regulate biological activities, such as cell proliferation, cell viability, induction of ROS production, ER stress, and apoptosis via modulation of cellular mechanisms in many cancers. Many natural products isolated from marine species require further study to elucidate the efficacy of their biological activity and anticancer effects. In this review, we summarize the biological properties and anticancer effects of diverse natural products extracted from marine organisms and their roles in tumor therapy. Cancer is one of the leading causes of death and an economic burden worldwide (1). Cancer involves an abnormal proliferation of cells and tissues, and is affected by various risk factors such as age, diet, genetics, and environmental factors (2, 3). It is also caused by the mutation of several cancer-related genes called tumor suppressors and oncogenes (4). Cancer also presents the ability of metastasis and recurrence, which are difficult to treat (5). Although conventional anticancer therapy includes both chemotherapy to induce apoptosis of target cancer cells and surgical therapy to remove tumors, these methods are limited by issues of therapeutic efficacy, safety, and side effects. Thus, it is necessary to develop novel strategies for cancer therapy, and natural products (NPs) are a promising source for novel drug development because they show diverse biological activities and anticancer effects via inhibition of tumor growth by interacting with several signaling pathways (6, 7). NPs have been a useful source of bioactive compounds and play an important role in the discovery and development of drugs. Most NPs, originated from terrestrial microbes, fungi, and plants, have been discovered to possess many pharmacologically active factors and used to treat several human diseases. Some of these are utilized as clinically valuable drugs for anticancer therapy (8-10). However, marine organisms have recently attracted substantial attention because 70% of the earth is covered by water, representing 95% of biodiversity (11-13). NPs derived from marine organisms have been researched for novel bioactive secondary metabolites due to their diverse pharmacological activities. Marine environments are estimated to harbor more than one million species and one billion different types of marine microbes (14). Today, around 28,000 new compounds isolated from marine species, such as algae, seaweed, sponges, and starfish, have been reported, and this species diversity provides a diverse array of secondary metabolic products (15, 16). In this review, we present NPs derived from marine environments, and summari...

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Autophagy is an important event for low-dose cytarabine treatment in acute myeloid leukemia cells

Cited by 27 publications

References 22 publications

Curcumin and tetrahydrocurcumin induce cell death in Ara‐C‐resistant acute myeloid leukemia

Curcumin and tetrahydrocurcumin induce cell death in Ara‐C‐resistant acute myeloid leukemia

Caspase-3 controls AML1-ETO–driven leukemogenesis via autophagy modulation in a ULK1-dependent manner

Therapeutic Application of Diverse Marine-derived Natural Products in Cancer Therapy

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