PARK2 promotes mitochondrial pathway of apoptosis and antimicrotubule drugs chemosensitivity via degradation of phospho-BCL-2

: Resistance of cancer cells to therapy is a challenge for achieving an appropriate therapeutic outcome. Cancer (stem) cells possess several mechanisms for increasing their survival following exposure to toxic agents such as chemotherapy drugs, radiation as well as immunotherapy. Evidences show that apoptosis plays a key role in response of cancer (stem) cells and their multi drug resistance. Modulation of both intrinsic and extrinsic pathways of apoptosis can increase efficiency of tumor response and amplify the therapeutic effect of radiotherapy, chemotherapy, targeted therapy and also immunotherapy. To date, several agents as adjuvant have been proposed to overcome resistance of cancer cells to apoptosis. Natural products are interesting because of low toxicity on normal tissues. Resveratrol is a natural herbal agent that has shown interesting anti-cancer properties. It has been shown to kill cancer cells selectively, while protecting normal cells. Resveratrol can augment reduction/oxidation (redox) reactions, thus increases the production of ceramide and the expression of apoptosis receptors such as Fas ligand (FasL). Resveratrol also triggers some pathways which induce mitochondrial pathway of apoptosis. On the other hand, resveratrol has an inhibitory effect on anti-apoptotic mediators such as nuclear factor κ B (NFκB), cyclooxygenase-2 (COX-2), phosphatidylinositol 3–kinase (PI3K) and mTOR. In this review, we explain the modulatory effects of resveratrol on apoptosis, which can augment the therapeutic efficiency of anti-cancer drugs or radiotherapy.

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Zearalenone induces apoptosis of rat Sertoli cells through Fas-Fas ligand and mitochondrial pathway

Environmental Toxicology ◽

10.1002/tox.22696 ◽

2019 ◽

Vol 34 (4) ◽

pp. 424-433 ◽

Cited By ~ 7

Author(s):

Guodong Cai ◽

Mengxue Si ◽

Xi Li ◽

Hui Zou ◽

Jianhong Gu ◽

...

Keyword(s):

Sertoli Cells ◽

Fas Ligand ◽

Mitochondrial Pathway

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Novel Hybrid Compounds Containing Benzofuroxan and Aminothiazole Scaffolds: Synthesis and Evaluation of Their Anticancer Activity

International Journal of Molecular Sciences ◽

10.3390/ijms22147497 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7497

Author(s):

Elena Chugunova ◽

Gabriele Micheletti ◽

Dario Telese ◽

Carla Boga ◽

Daut Islamov ◽

...

Keyword(s):

Anticancer Agents ◽

Normal Liver ◽

Mitochondrial Pathway ◽

Reaction Pathways ◽

Aromatic Nucleophilic Substitution ◽

X Ray ◽

Hybrid Compounds ◽

Aromatic Nucleophilic Substitution Reaction ◽

Further Development

A series of novel hybrid compounds containing benzofuroxan and 2-aminothiazole moieties are synthesized via aromatic nucleophilic substitution reaction. Possible reaction pathways have been considered quantum-chemically, which allowed us to suggest the most probable products. The quantum chemical results have been proved by X-ray data on one compound belonging to the synthesized series. It was shown that the introduction of substituents to both the thiazole and amine moieties of the compounds under study strongly influences their UV/Vis spectra. Initial substances and obtained hybrid compounds have been tested in vitro as anticancer agents. Target compounds showed selectivity towards M-HeLa tumor cell lines and were found to be more active than starting benzofuroxan and aminothiazoles. Furthermore, they are considerably less toxic to normal liver cells compared to Тamoxifen. The mechanism of action of the studied compounds can be associated with the induction of apoptosis, which proceeds along the mitochondrial pathway. Thus, new hybrids of benzofuroxan are promising candidates for further development as anticancer agents.

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Identification of a new natural biflavonoids against breast cancer cells induced ferroptosis via the mitochondrial pathway

Bioorganic Chemistry ◽

10.1016/j.bioorg.2021.104744 ◽

2021 ◽

Vol 109 ◽

pp. 104744

Author(s):

Yang Xie ◽

Xi Zhou ◽

Jing Li ◽

Xiao-Chang Yao ◽

Wan-Li Liu ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Mitochondrial Pathway

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Caffeic Acid Induces Apoptosis in Human Cervical Cancer Cells Through the Mitochondrial Pathway

Taiwanese Journal of Obstetrics and Gynecology ◽

10.1016/s1028-4559(10)60092-7 ◽

2010 ◽

Vol 49 (4) ◽

pp. 419-424 ◽

Cited By ~ 43

Author(s):

Wei-Chun Chang ◽

Ching-Hung Hsieh ◽

Meen-Woon Hsiao ◽

Wu-Chou Lin ◽

Yao-Ching Hung ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Caffeic Acid ◽

Mitochondrial Pathway ◽

Cervical Cancer Cells ◽

Human Cervical Cancer Cells ◽

Human Cervical Cancer

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8a, a New Acridine Antiproliferative and Pro-Apoptotic Agent Targeting HDAC1/DNMT1

International Journal of Molecular Sciences ◽

10.3390/ijms22115516 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5516

Author(s):

Qiting Zhang ◽

Ziyan Wang ◽

Xinyuan Chen ◽

Haoxiang Qiu ◽

Yifan Gu ◽

...

Keyword(s):

Histone Deacetylase ◽

Dna Methyltransferase ◽

Hdac Inhibitors ◽

Mitochondrial Pathway ◽

Epigenetic Therapy ◽

Protein Interaction Data ◽

Dependent Manner ◽

Histone Deacetylase 1 ◽

Histiocytic Lymphoma ◽

Dose Dependent

Epigenetic therapy using histone deacetylase (HDAC) inhibitors has become an attractive project in new drug development. However, DNA methylation and histone acetylation are important epigenetic ways to regulate the occurrence and development of leukemia. Given previous studies, N-(2-aminophenyl)benzamide acridine (8a), as a histone deacetylase 1 (HDAC1) inhibitor, induces apoptosis and shows significant anti-proliferative activity against histiocytic lymphoma U937 cells. HDAC1 plays a role in the nucleus, which we confirmed by finding that 8a entered the nucleus. Subsequently, we verified that 8a mainly passes through the endogenous (mitochondrial) pathway to induce cell apoptosis. From the protein interaction data, we found that 8a also affected the expression of DNA methyltransferase 1 (DNMT1). Therefore, an experiment was performed to assess the binding of 8a to DNMT1 at the molecular and cellular levels. We found that the binding strength of 8a to DNMT1 enhanced in a dose-dependent manner. Additionally, 8a inhibits the expression of DNMT1 mRNA and its protein. These findings suggested that the anti-proliferative and pro-apoptotic activities of 8a against leukemia cells were achieved by targeting HDAC1 and DNMT1.

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