Cisplatin / TumCCA Cancer Research Results

Cisplatin, Cisplatin: Click to Expand ⟱
Features:
Cisplatin is a chemotherapy medication used to treat various types of cancer. It is a platinum-based drug that works by interfering with the DNA of cancer cells, preventing them from reproducing and ultimately leading to cell death.
Cisplatin (cis-diamminedichloroplatinum II; CDDP) is a platinum-based chemotherapeutic agent that forms covalent DNA crosslinks, primarily intrastrand adducts at adjacent guanine bases. These distort DNA structure, block replication and transcription, and activate DNA damage response pathways (ATM/ATR → p53), leading to cell-cycle arrest and apoptosis. Secondary mechanisms include ROS generation, stress MAPK activation, and modulation of NF-κB. Clinical resistance frequently involves enhanced DNA repair (ERCC1/NER), altered drug transport (CTR1, ATP7A/B), and increased antioxidant defenses. Major toxicities include nephrotoxicity, ototoxicity, and peripheral neuropathy.

Rank Pathway / Axis Cancer / Tumor Context Normal Tissue Context TSF Primary Effect Notes / Interpretation
1 DNA crosslink formation (intrastrand adducts) DNA adducts ↑; replication block ↑ Normal dividing cells also affected P, R, G Direct DNA cytotoxicity Cisplatin forms covalent intrastrand crosslinks (primarily at adjacent guanines), distorting DNA and blocking replication and transcription.
2 DNA damage response (ATM / ATR → p53) Checkpoint activation ↑; p53 signaling ↑ ↔ (toxicity in proliferating tissues) R, G Damage signaling cascade DNA distortion activates ATM/ATR pathways leading to p53-mediated cell-cycle arrest and apoptosis.
3 Intrinsic apoptosis (mitochondrial pathway) Bax ↑; Bcl-2 ↓; caspase-9/3 ↑ Nephrotoxicity & ototoxicity risk G Execution of cell death Persistent DNA damage triggers mitochondrial outer membrane permeabilization and caspase activation.
4 Cell-cycle arrest (G2/M emphasis) G2/M arrest ↑ ↔ G Cytostasis → apoptosis Cells accumulate in G2/M phase due to unrepaired DNA lesions.
5 ROS generation / oxidative stress ROS ↑ (secondary mechanism) Oxidative injury ↑ (kidney, cochlea) R, G Stress amplification Cisplatin increases mitochondrial ROS and oxidative stress, contributing to cytotoxicity and organ toxicity.
6 MAPK signaling (JNK / p38 activation) Stress MAPK activation ↑ ↔ R, G Stress-response signaling JNK and p38 activation contribute to apoptosis and stress signaling.
7 NF-κB activation (resistance axis) NF-κB ↑ may promote survival ↔ R, G Resistance modulation NF-κB activation can reduce sensitivity; inhibition enhances cytotoxicity in some models.
8 DNA repair pathways (NER / ERCC1) NER ↑ → resistance — G Resistance determinant Nucleotide excision repair (ERCC1) removes platinum adducts; high ERCC1 correlates with resistance.
9 Drug transport (CTR1 uptake; ATP7A/B efflux) CTR1 ↓ or ATP7A/B ↑ → resistance — G Exposure constraint Copper transporters influence intracellular cisplatin accumulation and resistance.
10 Clinical toxicity profile — Nephrotoxicity, ototoxicity, neurotoxicity — Translation constraint Major dose-limiting toxicities arise from DNA damage and oxidative stress in normal tissues.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (DNA aquation and initial adduct formation)
  • R: 30 min–3 hr (checkpoint activation / stress signaling)
  • G: >3 hr (apoptosis, phenotype outcomes, resistance development)
TumCCA, Tumor cell cycle arrest: Click to Expand ⟱
Source:
Type:
Tumor cell cycle arrest refers to the process by which cancer cells stop progressing through the cell cycle, which is the series of phases that a cell goes through to divide and replicate. This arrest can occur at various checkpoints in the cell cycle, including the G1, S, G2, and M phases. S, G1, G2, and M are the four phases of mitosis.
Scientific Papers found: Click to Expand⟱
564- ART/DHA,  Cisplatin,    Dihydroartemisinin as a Putative STAT3 Inhibitor, Suppresses the Growth of Head and Neck Squamous Cell Carcinoma by Targeting Jak2/STAT3 Signaling
- in-vitro, NA, HN30
JAK2↓, STAT3↓, MMP2↓, MMP9↓, Mcl-1↓, Bcl-xL↓, cycD1/CCND1↓, VEGF↓, TumCCA↑, ChemoSen↑,
5651- BNL,  Cisplatin,    Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway
- in-vitro, GBM, U251 - in-vitro, GBM, U87MG
ChemoSen↑, tumCV↓, TumCCA↑, Apoptosis↑, ROS↑, DNAdam↑, ATR↑, ATM↑, P53↑, Histones↑, eff↓, Casp3↑, Casp7↑, Casp9↑,
1450- Bos,  Cisplatin,    3-Acetyl-11-keto-β-boswellic acid (AKBA) induced antiproliferative effect by suppressing Notch signaling pathway and synergistic interaction with cisplatin against prostate cancer cells
- in-vitro, Pca, DU145
ROS↑, MMP↓, Casp↑, Apoptosis↑, Bax:Bcl2↑, TumCCA?, cycD1/CCND1↓, CDK4↓, P21↑, p27↑, NOTCH↓, ChemoSen↑,
5965- CEL,  Cisplatin,    Celecoxib enhances anticancer effect of cisplatin and induces anoikis in osteosarcoma via PI3K/Akt pathway
- in-vitro, OS, MG63
COX2↓, ChemoSen↑, MDR1↓, MRP1↓, E-cadherin↓, β-catenin/ZEB1↓, Apoptosis↑, TumCCA↑, TumCG↓, P-gp↓, PI3K↓, Akt↓,
1411- CUR,  Cisplatin,    Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects
- Review, Var, NA
ChemoSen↑, *ROS↓, *NF-kB↓, TumCCA↑,
1966- GamB,  Cisplatin,    Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non-small-cell lung cancer through suppressing NF-κB and MAPK/HO-1 signalling
- in-vitro, Lung, A549 - in-vitro, Lung, NCIH1299
TumCCA↑, PARP↑, eff↑, ROS↑, ChemoSen↑,
805- GAR,  Cisplatin,  PacT,    Garcinol Exhibits Anti-Neoplastic Effects by Targeting Diverse Oncogenic Factors in Tumor Cells
- Review, NA, NA
ERK↓, PI3K/Akt↓, Wnt/(β-catenin)↓, STAT3↓, NF-kB↓, ChemoSen↑, COX2↓, Casp3↑, Casp9↑, BAX↑, Bcl-2↓, VEGF↓, TGF-β↓, HATs↓, E-cadherin↑, Vim↓, Zeb1↓, ZEB2↓, Let-7↑, MMP9↓, TumCCA↑, ROS↑, MMP↓, IL6↓, NOTCH1↓,
2008- SK,  Cisplatin,    Enhancement of cisplatin-induced colon cancer cells apoptosis by shikonin, a natural inducer of ROS in vitro and in vivo
- in-vitro, CRC, HCT116 - in-vivo, NA, NA
ChemoSen↑, selectivity↑, i-ROS↑, DNAdam↑, MMP↓, TumCCA↑, eff↓, *toxicity↓,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 4,   i-ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 3,  

Core Metabolism/Glycolysis ⓘ

Histones↑, 1,   PI3K/Akt↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 3,   BAX↑, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp↑, 1,   Casp3↑, 2,   Casp7↑, 1,   Casp9↑, 2,   Mcl-1↓, 1,   p27↑, 1,  

Transcription & Epigenetics ⓘ

HATs↓, 1,   tumCV↓, 1,  

DNA Damage & Repair ⓘ

ATM↑, 1,   ATR↑, 1,   DNAdam↑, 2,   P53↑, 1,   PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 1,   cycD1/CCND1↓, 2,   P21↑, 1,   TumCCA?, 1,   TumCCA↑, 7,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   Let-7↑, 1,   NOTCH↓, 1,   NOTCH1↓, 1,   PI3K↓, 1,   STAT3↓, 2,   TumCG↓, 1,   Wnt/(β-catenin)↓, 1,  

Migration ⓘ

E-cadherin↓, 1,   E-cadherin↑, 1,   MMP2↓, 1,   MMP9↓, 2,   TGF-β↓, 1,   Vim↓, 1,   Zeb1↓, 1,   ZEB2↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 2,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IL6↓, 1,   JAK2↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 8,   eff↓, 2,   eff↑, 1,   MDR1↓, 1,   MRP1↓, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  
Total Targets: 59

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Functional Outcomes ⓘ

toxicity↓, 1,  
Total Targets: 3

Scientific Paper Hit Count for: TumCCA, Tumor cell cycle arrest
8 Cisplatin
1 Artemisinin
1 borneol
1 Boswellia (frankincense)
1 Celecoxib
1 Curcumin
1 Gambogic Acid
1 Garcinol
1 Paclitaxel
1 Shikonin
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:197  Target#:322  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page