The Cytoprotective, Cytotoxic and Nonprotective Functional Forms of Autophagy Induced by Microtubule Poisons in Tumor Cells—Implications for Autophagy Modulation as a Therapeutic Strategy
Abstract
:1. Introduction
2. Autophagy and Cancer
3. Microtubules and Microtubule Poisons
4. Direct Involvement of Microtubules in Autophagy
4.1. Colchicine Site
4.2. Vinca Alkaloid Site
4.3. Taxane Site
4.4. Epothilone Site
4.5. Laulimalide/Peloruside Site
5. Summary and Overview
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Agents | Cancer Type | Autophagy | Autophagy Inhibitor | Autophagy and Cell Death | Ref. |
---|---|---|---|---|---|
Colchicine | A549 lung cancer cell line | Autophagy induction (associated with senescence) | 3-MA | Cytoprotective autophagy | [50] |
Colchicine derivative “JG-03-14” | MCF-7 and MDA-MB-231 breast cancer cells | Autophagy induction | N/A | Cytotoxic autophagy | [52] |
Colchicine derivative “JG-03-14” | B16/F10 melanoma and HCT-116 colon cancer cells | Autophagy induction | CQ and Baf A1 | Cytotoxic autophagy | [53] |
Colchicine derivative “Green 1” | PANC-1 pancreatic cancer and E6-1 or Jurkat acute T cell leukemia cell lines | Autophagy induction | N/A | Cytotoxic autophagy | [54] |
Colchicine derivative “AD1” | U87MG and U373MG human malignant glioblastoma cell lines | Autophagy induction | N/A | Cytotoxic autophagy | [55] |
Podophyllotoxin acetate | A549 and NCI-H1299 human non-small cell lung cancer cell lines | Autophagy induction | N/A | Cytotoxic autophagy | [60] |
Podophyllotoxin derivative “Da-1” | K562/VCR chronic myeloid leukemia cell lines | Autophagy induction | N/A | Cytotoxic autophagy | [61] |
Podophyllotoxin derivative “OAMDP” | HepG2 hepatoma cell line | Autophagy induction | N/A | Cytotoxic autophagy | [62] |
Combretastatin A-4 | MDA-MB-231 breast tumor cells, SGC-7901 human gastric tumor cells and SMMC-7721 human hepatocellular carcinoma cells | Autophagy induction | In vitro; 3-MA/Baf A1/siRNAs against Atg5 and Beclin 1 genes/BCL2 inhibitor (ABT-737) JNK inhibitor or JNK siRNA In vivo; 3-MA | Cytoprotective autophagy | [67] |
Combretastatin A-4 | CT-26 and HT-29 adenocarcinoma cell lines | Autophagy induction | 3-MA, Baf A1 | Non-protective autophagy in CT-26 cell line, Cytoprotective autophagy in HT-29 cell line | [68] |
Combretastatin A-4 | SJSA and MG63 human osteosarcoma cell lines | Autophagy induction | CQ | Cytoprotective autophagy | [69] |
Combretastatin A-4 phosphate | PC3 prostate cancer xenografts | Autophagy induction | autophagy-defective PC3 prostate cancer xenografts (developed with retrovirally transducing PC-3 cells with ATG4BC74A) | Cytoprotective autophagy | [71,72] |
Vinblastine | Ehrlich ascites tumor cells | Autophagy inhibition with autophagic vacuoles accumulation | N/A | N/A | [80] |
Vinblastine | HepG2 human hepatocarcinoma and LS174T colon cancer cell lines | blocked autophagy maturation | CQ | Autophagy inhibition | [82] |
Vincristine | Neuroblastoma cell lines | Autophagy induction | In vivo; ATG5 knockdown In vivo; HCQ | Cytoprotective autophagy | [84] |
Vincristine | Eca-109/VCR esophagus cancer cell line | Autophagy induction | autophagy inhibitor “4d” | Cytoprotective autophagy | [85] |
Vincristine | REH and Nalm-6 pre-B acute lymphoblastic leukemia (ALL) cell lines | Autophagy induction | CQ | Cytoprotective autophagy | [86] |
Vincristine | human retinoblastoma cells | Autophagy induction | CQ, CD24 knockdown | Cytoprotective autophagy | [87] |
Vincristine | K562/ADM cell line | Autophagy induction | CQ reversed the inhibitory effect of MAT | MAT promote cytotoxic autophagy | [88] |
Vincristine | multiple myeloma cells | Autophagy induction | N/A | Cotylenin A promote cytotoxic autophagy | [89] |
Paclitaxel | breast cancer cells | Paclitaxel prevents autophagosome maturation and lysosome fusion in breast cancer cells | 3-MA | Activates apoptosis as a result of autophagic flux inhibition in cancer cells | [98] |
Paclitaxel | breast cancer cells | Paclitaxel alone did not induce autophagy in breast cancer cells, it enhanced ARHI-induced autophagy. | N/A | When ARHI was re-expressed in breast cancer cells treated with paclitaxel, the growth inhibitory effect of paclitaxel was enhanced in both the cell culture and the xenografts. | [97] |
Paclitaxel | A2780, 3AO, and SKOV3 ovarian cancer cells | Paclitaxel increases autophagosome formation and autophagic flux | Beclin-1 deficiency | Cytoprotective autophagy | [99] |
Paclitaxel | A549 cells; U87, PC3 and HT-29 cells | Autophagy induction (no p62/SQSTM1 detected) | 3-MA /Beclin 1 siRNA | Cytoprotective autophagy | [100] |
Docetaxel | LNCaP, PC3, and DU145 | Autophagy induction | 3-MA | Non-protective autophagy | [105] |
Docetaxel | docetaxel resistant prostate cancer cell lines | Autophagy induction | N/A | Non-protective autophagy | [104] |
Docetaxel | prostate cancer cells | Autophagy induction | 3-MA | Cytoprotective autophagy | [106] |
Epothilone A and Epothilone B | ovarian cancer cells | Autophagy induction | Baf A1 | Cytoprotective autophagy | [113] |
Ixabepilone | hepatic carcinoma, glioma cells and breast cancer cells | Autophagy induction | In vitro: CQ, 3-MA, beclin-1 si RNA In vivo: CQ | Cytoprotective autophagy | [116] |
Ixabepilone | MDA-MB-231 and SUM159 cells | Ixabepilone increased p62/SQSTM1 expression, Ixabepilone either reduced or had no effect on the basal levels of LC3b-II | N/A | N/A | [115] |
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Xu, J.; Elshazly, A.M.; Gewirtz, D.A. The Cytoprotective, Cytotoxic and Nonprotective Functional Forms of Autophagy Induced by Microtubule Poisons in Tumor Cells—Implications for Autophagy Modulation as a Therapeutic Strategy. Biomedicines 2022, 10, 1632. https://doi.org/10.3390/biomedicines10071632
Xu J, Elshazly AM, Gewirtz DA. The Cytoprotective, Cytotoxic and Nonprotective Functional Forms of Autophagy Induced by Microtubule Poisons in Tumor Cells—Implications for Autophagy Modulation as a Therapeutic Strategy. Biomedicines. 2022; 10(7):1632. https://doi.org/10.3390/biomedicines10071632
Chicago/Turabian StyleXu, Jingwen, Ahmed M. Elshazly, and David A. Gewirtz. 2022. "The Cytoprotective, Cytotoxic and Nonprotective Functional Forms of Autophagy Induced by Microtubule Poisons in Tumor Cells—Implications for Autophagy Modulation as a Therapeutic Strategy" Biomedicines 10, no. 7: 1632. https://doi.org/10.3390/biomedicines10071632
APA StyleXu, J., Elshazly, A. M., & Gewirtz, D. A. (2022). The Cytoprotective, Cytotoxic and Nonprotective Functional Forms of Autophagy Induced by Microtubule Poisons in Tumor Cells—Implications for Autophagy Modulation as a Therapeutic Strategy. Biomedicines, 10(7), 1632. https://doi.org/10.3390/biomedicines10071632