H2O2 enhances the anticancer activity of TMPyP4 by ROS-mediated mitochondrial dysfunction and DNA damage

Objective: To overcome the disadvantages of cisplatin, numerous platinum (Pt) complexes have been prepared. However, the anticancer activity and mechanism of Pt(II) complexed with 2-benzoylpyridine [Pt(II)- Bpy]: [PtCl2(DMSO)L] (DMSO = dimethyl sulfoxide, L = 2-benzoylpyridine) in cancer cells remain unknown. Methods: Pt(II)-Bpy was synthesized and characterized by spectrum analysis. Its anticancer activity and underlying mechanisms were demonstrated at the cellular, molecular, and in vivo levels. Results: Pt(II)-Bpy inhibited tumor cell growth, especially HepG2 human liver cancer cells, with a halfmaximal inhibitory concentration of 9.8±0.5μM, but with low toxicity in HL-7702 normal liver cells. Pt(II)- Bpy induced DNA damage, which was demonstrated through a marked increase in the expression of cleavedpoly (ADP ribose) polymerase (PARP) and gamma-H2A histone family member X and a decrease in PARP expression. The interaction of Pt(II)-Bpy with DNA at the molecular level was most likely through an intercalation mechanism, which might be evidence of DNA damage. Pt(II)-Bpy initiated cell cycle arrest at the S phase in HepG2 cells. It also caused severe loss of the mitochondrial membrane potential; a decrease in the expression of caspase-9 and caspase-3; an increase in reactive oxygen species levels; the release of cytochrome c and apoptotic protease activation factor; and the activation of caspase-9 and caspase-3 in HepG2 cells, which in turn resulted in apoptosis. Meanwhile, changes in p53 and related proteins were observed including the upregulation of p53, the phosphorylation of p53, p21, B-cell lymphoma-2-associated X protein, and NOXA; and the downregulation of B-cell lymphoma 2. Moreover, Pt(II)-Bpy displayed marked inhibitory effects on tumor growth in the HepG2 nude mouse model. Conclusion: Pt(II)-Bpy is a potential candidate for cancer chemotherapy.

Download Full-text

Piperlongumine inhibits migration and proliferation of castration-resistant prostate cancer cells via triggering persistent DNA damage

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03369-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ding-fang Zhang ◽

Zhi-chun Yang ◽

Jian-qiang Chen ◽

Xiang-xiang Jin ◽

Yin-da Qiu ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Dna Damage ◽

Cell Adhesion ◽

Anticancer Activity ◽

Cancer Cells ◽

Castration Resistant Prostate Cancer ◽

Prostate Cancer Cells ◽

Dna Damage And Repair ◽

Castration Resistant

Abstract Background Metastatic castration-resistant prostate cancer (CRPC) is the leading cause of death among men diagnosed with prostate cancer. Piperlongumine (PL) is a novel potential anticancer agent that has been demonstrated to exhibit anticancer efficacy against prostate cancer cells. However, the effects of PL on DNA damage and repair against CRPC have remained unclear. The aim of this study was to further explore the anticancer activity and mechanisms of action of PL against CRPC in terms of DNA damage and repair processes. Methods The effect of PL on CRPC was evaluated by MTT assay, long-term cell proliferation, reactive oxygen species assay, western blot assay, flow cytometry assay (annexin V/PI staining), β-gal staining assay and DAPI staining assay. The capacity of PL to inhibit the invasion and migration of CRPC cells was assessed by scratch-wound assay, cell adhesion assay, transwell assay and immunofluorescence (IF) assay. The effect of PL on DNA damage and repair was determined via IF assay and comet assay. Results The results showed that PL exhibited stronger anticancer activity against CRPC compared to that of taxol, cisplatin (DDP), doxorubicin (Dox), or 5-Fluorouracil (5-FU), with fewer side effects in normal cells. Importantly, PL treatment significantly decreased cell adhesion to the extracellular matrix and inhibited the migration of CRPC cells through affecting the expression and distribution of focal adhesion kinase (FAK), leading to concentration-dependent inhibition of CRPC cell proliferation and concomitantly increased cell death. Moreover, PL treatment triggered persistent DNA damage and provoked strong DNA damage responses in CRPC cells. Conclusion Collectively, our findings demonstrate that PL potently inhibited proliferation, migration, and invasion of CRPC cells and that these potent anticancer effects were potentially achieved via triggering persistent DNA damage in CRPC cells.

Download Full-text

Amphetamines promote mitochondrial dysfunction and DNA damage in pulmonary hypertension

JCI Insight ◽

10.1172/jci.insight.90427 ◽

2017 ◽

Vol 2 (2) ◽

Cited By ~ 30

Author(s):

Pin-I Chen ◽

Aiqin Cao ◽

Kazuya Miyagawa ◽

Nancy F. Tojais ◽

Jan K. Hennigs ◽

...

Keyword(s):

Dna Damage ◽

Pulmonary Hypertension ◽

Mitochondrial Dysfunction

Download Full-text

Genomic and functional integrity of the hematopoietic system requires tolerance of oxidative DNA lesions

Blood ◽

10.1182/blood-2017-01-764274 ◽

2017 ◽

Vol 130 (13) ◽

pp. 1523-1534 ◽

Cited By ~ 14

Author(s):

Ana Martín-Pardillos ◽

Anastasia Tsaalbi-Shtylik ◽

Si Chen ◽

Seka Lazare ◽

Ronald P. van Os ◽

...

Keyword(s):

Dna Damage ◽

Mitochondrial Dysfunction ◽

Replication Stress ◽

Precursor Cells ◽

Dna Lesions ◽

Hematopoietic Stem ◽

Hematopoietic System ◽

Functional Integrity ◽

Key Points

Key Points Tolerance of oxidative DNA lesions ensures the genomic and functional integrity of hematopoietic stem and precursor cells. Endogenous DNA damage–induced replication stress is associated with mitochondrial dysfunction.

Download Full-text

Dietary zerumbone from shampoo ginger: new insights into its antioxidant and anticancer activity

Food & Function ◽

10.1039/c8fo02395f ◽

2019 ◽

Vol 10 (3) ◽

pp. 1629-1642 ◽

Cited By ~ 5

Author(s):

A. Rosa ◽

D. Caprioglio ◽

R. Isola ◽

M. Nieddu ◽

G. Appendino ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Lipid Profile ◽

Anticancer Activity ◽

Cancer Cells ◽

Total Lipid ◽

Lipid Droplets

The dietary sesquiterpene dienone zerumbone (ZER) selectively targets cancer cells, inducing mitochondrial dysfunction, apoptosis, modulation of the total lipid profile, and accumulation of cytosolic lipid droplets.

Download Full-text