Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy
Anticancer drugs induce apoptotic and non-apoptotic cell death in various cancer types. The signaling pathways for anticancer drug-induced apoptotic cell death have been shown to differ between drug-sensitive and drug-resistant cells. In atypical multidrug-resistant leukemia cells, the <i>c-Ju...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/5/984 |
| _version_ | 1797264714736074752 |
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| author | Ryungsa Kim Takanori Kin William T. Beck |
| author_facet | Ryungsa Kim Takanori Kin William T. Beck |
| author_sort | Ryungsa Kim |
| collection | DOAJ |
| description | Anticancer drugs induce apoptotic and non-apoptotic cell death in various cancer types. The signaling pathways for anticancer drug-induced apoptotic cell death have been shown to differ between drug-sensitive and drug-resistant cells. In atypical multidrug-resistant leukemia cells, the <i>c-Jun</i>/activator protein 1 (AP-1)/<i>p53</i> signaling pathway leading to apoptotic death is altered. Cancer cells treated with anticancer drugs undergo <i>c-Jun</i>/AP-1–mediated apoptotic death and are involved in <i>c-Jun</i> N-terminal kinase activation and growth arrest- and DNA damage-inducible gene 153 (<i>Gadd153</i>)/CCAAT/enhancer-binding protein homologous protein pathway induction, regardless of the <i>p53</i> genotype. <i>Gadd153</i> induction is associated with mitochondrial membrane permeabilization after anticancer drug treatment and involves a coupled endoplasmic reticulum stress response. The induction of apoptosis by anticancer drugs is mediated by the intrinsic pathway (cytochrome c, Cyt c) and subsequent activation of the caspase cascade via proapoptotic genes (e.g., <i>Bax</i> and <i>Bcl-xS</i>) and their interactions. Anticancer drug-induced apoptosis involves caspase-dependent and caspase-independent pathways and occurs via intrinsic and extrinsic pathways. The targeting of antiapoptotic genes such as <i>Bcl-2</i> enhances anticancer drug efficacy. The modulation of apoptotic signaling by <i>Bcl-xS</i> transduction increases the sensitivity of multidrug resistance-related protein-overexpressing epidermoid carcinoma cells to anticancer drugs. The significance of autophagy in cancer therapy remains to be elucidated. In this review, we summarize current knowledge of cancer cell death-related signaling pathways and their alterations during anticancer drug treatment and discuss potential strategies to enhance treatment efficacy. |
| first_indexed | 2024-04-25T00:33:18Z |
| format | Article |
| id | doaj.art-5853c31c04e54848b8c89c4f296a8ba6 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-04-25T00:33:18Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5853c31c04e54848b8c89c4f296a8ba62024-03-12T16:41:05ZengMDPI AGCancers2072-66942024-02-0116598410.3390/cancers16050984Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to TherapyRyungsa Kim0Takanori Kin1William T. Beck2Department of Breast Surgery, Hiroshima Mark Clinic, 1-4-3F, 2-Chome Ohte-machi, Naka-ku, Hiroshima 730-0051, JapanDepartment of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USAAnticancer drugs induce apoptotic and non-apoptotic cell death in various cancer types. The signaling pathways for anticancer drug-induced apoptotic cell death have been shown to differ between drug-sensitive and drug-resistant cells. In atypical multidrug-resistant leukemia cells, the <i>c-Jun</i>/activator protein 1 (AP-1)/<i>p53</i> signaling pathway leading to apoptotic death is altered. Cancer cells treated with anticancer drugs undergo <i>c-Jun</i>/AP-1–mediated apoptotic death and are involved in <i>c-Jun</i> N-terminal kinase activation and growth arrest- and DNA damage-inducible gene 153 (<i>Gadd153</i>)/CCAAT/enhancer-binding protein homologous protein pathway induction, regardless of the <i>p53</i> genotype. <i>Gadd153</i> induction is associated with mitochondrial membrane permeabilization after anticancer drug treatment and involves a coupled endoplasmic reticulum stress response. The induction of apoptosis by anticancer drugs is mediated by the intrinsic pathway (cytochrome c, Cyt c) and subsequent activation of the caspase cascade via proapoptotic genes (e.g., <i>Bax</i> and <i>Bcl-xS</i>) and their interactions. Anticancer drug-induced apoptosis involves caspase-dependent and caspase-independent pathways and occurs via intrinsic and extrinsic pathways. The targeting of antiapoptotic genes such as <i>Bcl-2</i> enhances anticancer drug efficacy. The modulation of apoptotic signaling by <i>Bcl-xS</i> transduction increases the sensitivity of multidrug resistance-related protein-overexpressing epidermoid carcinoma cells to anticancer drugs. The significance of autophagy in cancer therapy remains to be elucidated. In this review, we summarize current knowledge of cancer cell death-related signaling pathways and their alterations during anticancer drug treatment and discuss potential strategies to enhance treatment efficacy.https://www.mdpi.com/2072-6694/16/5/984anticancer drugsignaling pathwaycell deathantitumor immunitycancer cell |
| spellingShingle | Ryungsa Kim Takanori Kin William T. Beck Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy Cancers anticancer drug signaling pathway cell death antitumor immunity cancer cell |
| title | Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy |
| title_full | Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy |
| title_fullStr | Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy |
| title_full_unstemmed | Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy |
| title_short | Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy |
| title_sort | impact of complex apoptotic signaling pathways on cancer cell sensitivity to therapy |
| topic | anticancer drug signaling pathway cell death antitumor immunity cancer cell |
| url | https://www.mdpi.com/2072-6694/16/5/984 |
| work_keys_str_mv | AT ryungsakim impactofcomplexapoptoticsignalingpathwaysoncancercellsensitivitytotherapy AT takanorikin impactofcomplexapoptoticsignalingpathwaysoncancercellsensitivitytotherapy AT williamtbeck impactofcomplexapoptoticsignalingpathwaysoncancercellsensitivitytotherapy |