Phytochemical Modulation of Apoptosis and Autophagy: Strategies to Overcome Chemoresistance in Leukemic Stem Cells in the Bone Marrow Microenvironment

Owen, Helen; Appiah, Sandra S.; Hasan, Noor; Ghali, Lucy; Elayat, Ghada; Bell, Celia M.

doi:10.1016/bs.irn.2017.02.012

Cited by 24 publications

(12 citation statements)

References 97 publications

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“…Epidemiologic data suggest that CML incidence is one to two per 100,000 individuals, with 15–20% of adult leukemia cases being CML ( 2 ). While CML is commonly treated with tyrosine kinase inhibitors, an increase in drug resistance has been reported along with adverse side effects ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Liposome‑delivered baicalein induction of myeloid leukemia K562 cell death via reactive oxygen species generation

et al. 2018

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Baicalein (BL), a potential cancer chemopreventative flavone, has been reported to inhibit cancer cell growth by inducing apoptosis and causing cell cycle arrest in various human cancer cell models. Delivery of BL via nanoliposomes has been shown to improve its oral bioavailability and long-circulating property in vivo. However, the role of BL in the inhibition of human chronic myeloid leukemia (CML) K562 cell growth and its underlying mechanisms has yet to be elucidated. In the present study, BL was formulated into liposomes with different sizes to improve its solubility and stability. The cytotoxic and pro-apoptotic effects of free BL and liposomal BL were also evaluated. The results demonstrated that 100 nm liposomes were the most stable formulation when compared with 200 and 400 nm liposomes. Liposomal BL inhibited K562 cell growth as efficiently as free BL (prepared in DMSO), indicating that the liposome may be a potential vehicle to deliver BL for the treatment of CML. Flow cytometry analysis showed that there was significant (P<0.005) cell cycle arrest in the sub-G1 phase (compared with vehicle control), indicating cell apoptosis following 20 µM liposomal BL or free BL treatment of K562 cells for 48 h. The induction of cell apoptosis by all BL preparations was further confirmed through the staining of treated cells with Annexin V-fluorescein isothiocyanate/propidium iodide. A significant increase in reactive oxygen species (ROS) generation was observed in free BL and liposomal BL treated cells, with a higher level of ROS produced from those treated with free BL. This indicated that cell apoptosis induced by BL may be via ROS generation and liposome delivery may further extend the effect through its long-circulating property.

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Section: Introductionmentioning

confidence: 99%

Liposome‑delivered baicalein induction of myeloid leukemia K562 cell death via reactive oxygen species generation

et al. 2018

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“…Owing to this data, we believe that the diminished NF-κB activity demonstrated in this and separate (Xu et al, 2017) instances caused by wogonin comes through a modulatory effect on ciliary signaling. In addition to this data, it is known that wogonin has been demonstrated in separate instances to have inhibitory activity on SHH (Owen et al, 2017) and WNT signaling (Song et al, 2015), processes which are upregulated in osteoarthritis (Luyten et al, 2009;Chang et al, 2012) and mediated by the primary cilium. The fact that wogonin directly counters these pathways with strong connections to the primary cilia and possesses antiosteoarthritic activity strongly suggests that wogonin exerts some sort of corrective action on the primary cilia, and future research should focus on interactions between wogonin and ciliary homeostasis.…”

Section: Wogonin On the Primary Ciliummentioning

confidence: 76%

Topical Application of Wogonin Provides a Novel Treatment of Knee Osteoarthritis

et al. 2020

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Osteoarthritis (OA) is a degenerative joint disease characterized by joint pain, decreased functional mobility, and deformation of articular cartilage and consequentially diminishing quality of life. Wogonin (WG), a compound extracted from the Skullcap Baicalensis plant, has been shown to have anti‐inflammatory effects on the Toll‐like Receptor 4 (TLR‐4) inflammatory pathway and antioxidant properties via Nrf2. We have shown that TLR‐4 is a major receptor for pain in OA. In our study, we examined the pain reducing, anti‐inflammatory, and chondroprotective effects of WG when applied as a topical cream (TC). After destabilizing the menisci of mice to induce OA, we examined the severity and progression of OA with and without the topical application of WG. Using a running wheel to track mice activity, we found that mice with WG treatment were statistically more active than mice without WG treatment. OA progression analyzed using Modified Mankin and OARSI scoring showed a significant attenuation of OA severity among mice treated with WG. Immunohistochemistry revealed a significant decrease in protein expression of TGF‐β1, but no significant differences were found among the biomarkers HTRA1, MMP‐13, or BMP‐2, suggesting an alternative pathway of cartilage rescue. Support or Funding Information BYU Office of Research and Creative Works This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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“…Chemoresistance disrupts anticancer drug actions and renders therapy ineffective. Chemoresistance is induced by numerous factors, including inhibition of drug absorption ( 37 ), epigenetic modifications ( 38 ), cell cycle alterations ( 39 ) and inhibition of apoptosis ( 40 ). Accordingly, one of the critical factors mediating chemoresistance is inhibition of cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Human non‑small cell lung cancer cells can be sensitized to camptothecin by modulating autophagy

Chiu¹,

Hsu

et al. 2018

Int J Oncol

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Lung cancer is a prevalent disease and is one of the leading causes of mortality worldwide. Despite the development of various anticancer drugs, the prognosis of lung cancer is relatively poor. Metastasis of lung cancer, as well as chemoresistance, is associated with a high mortality rate for patients with lung cancer. Camptothecin (CPT) is a well-known anticancer drug, which causes cancer cell apoptosis via the induction of DNA damage; however, the cytotoxicity of CPT easily reaches a plateau at a relatively high dose in lung cancer cells, thus limiting its efficacy. The present study demonstrated that CPT may induce autophagy in two human non-small cell lung cancer cell lines, H1299 and H460. In addition, the results of a viability assay and Annexin V staining revealed that CPT-induced autophagy could protect lung cancer cells from programmed cell death. Conversely, the cytotoxicity of CPT was increased when autophagy was blocked by 3-methyladenine treatment. Furthermore, inhibition of autophagy enhanced the levels of CPT-induced DNA damage in the lung cancer cell lines. Accordingly, these findings suggested that autophagy exerts a protective role in CPT-treated lung cancer cells, and the combination of CPT with a specific inhibitor of autophagy may be considered a promising strategy for the future treatment of lung cancer.

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Phytochemical Modulation of Apoptosis and Autophagy: Strategies to Overcome Chemoresistance in Leukemic Stem Cells in the Bone Marrow Microenvironment

Cited by 24 publications

References 97 publications

Liposome‑delivered baicalein induction of myeloid leukemia K562 cell death via reactive oxygen species generation

Liposome‑delivered baicalein induction of myeloid leukemia K562 cell death via reactive oxygen species generation

Topical Application of Wogonin Provides a Novel Treatment of Knee Osteoarthritis

Human non‑small cell lung cancer cells can be sensitized to camptothecin by modulating autophagy

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