Cisplatin / Akt 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)
Akt, PKB-Protein kinase B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes; Akt2 is an important signaling molecule in the insulin signaling pathway. It is required to induce glucose transport.

Inhibitors:
-Curcumin: downregulate AKT phosphorylation and signaling.
-Resveratrol
-Quercetin: inhibit the PI3K/AKT pathway.
-Epigallocatechin Gallate (EGCG)
-Luteolin and Apigenin: inhibit AKT phosphorylation


Scientific Papers found: Click to Expand⟱
581- Api,  Cisplatin,    The natural flavonoid apigenin sensitizes human CD44+ prostate cancer stem cells to cisplatin therapy
- in-vitro, Pca, CD44+
Bcl-2↓, survivin↓, Casp8↑, P53↑, Sharpin↓, APAF1↑, p‑Akt↓, NF-kB↓, P21↑, Cyc↓, CDK2↓, CDK4/6↓, Snail↓, ChemoSen↑,
583- Api,  Cisplatin,    Apigenin suppresses GLUT-1 and p-AKT expression to enhance the chemosensitivity to cisplatin of laryngeal carcinoma Hep-2 cells: an in vitro study
- in-vitro, Laryn, HEp2
PI3K/Akt↓, GLUT1↓, Akt↓,
5181- BBR,  Cisplatin,    Berberine Improves Chemo-Sensitivity to Cisplatin by Enhancing Cell Apoptosis and Repressing PI3K/AKT/mTOR Signaling Pathway in Gastric Cancer
- in-vitro, GC, SGC-7901 - in-vitro, GC, BGC-823
tumCV↓, MDR1↓, ChemoSen↑, PI3K↓, Akt↓, mTOR↓,
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↓,
949- FIS,  ATAGJ,  Cisplatin,    Ai-Tong-An-Gao-Ji and Fisetin Inhibit Tumor Cell Growth in Rat CIBP Models by Inhibiting the AKT/HIF-1α Signaling Pathway
- in-vivo, BC, Walker256 - in-vitro, BC, Walker256
Akt↓, Hif1a↓, p‑Akt↓,
828- GAR,  Cisplatin,    Garcinol Alone and in Combination With Cisplatin Affect Cellular Behavior and PI3K/AKT Protein Phosphorylation in Human Ovarian Cancer Cells
- in-vitro, Ovarian, OVCAR-3
tumCV↓, cl‑PARP↑, cl‑Casp3↑, BAX↑, p‑PI3K↓, p‑Akt↓, NF-kB↓,
4920- PEITC,  Cisplatin,    PEITC restores chemosensitivity in cisplatin-resistant non-small cell lung cancer by targeting c-Myc/miR-424-5p
- vitro+vivo, NSCLC, A549
TumCG↓, ChemoSen↑, cMyc↓, PI3K↓, Akt↓, mTOR↓, BioAv↝, tumCV↓, ChemoSen↑,

Showing Research Papers: 1 to 7 of 7

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   PI3K/Akt↓, 1,  

Cell Death ⓘ

Akt↓, 5,   p‑Akt↓, 3,   APAF1↑, 1,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   cl‑Casp3↑, 1,   Casp8↑, 1,   survivin↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 3,  

DNA Damage & Repair ⓘ

P53↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   Cyc↓, 1,   P21↑, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↓, 2,   PI3K↓, 3,   p‑PI3K↓, 1,   TumCG↓, 2,  

Migration ⓘ

CDK4/6↓, 1,   E-cadherin↓, 1,   Sharpin↓, 1,   Snail↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   NF-kB↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,   ChemoSen↑, 5,   MDR1↓, 2,   MRP1↓, 1,  
Total Targets: 36

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Akt, PKB-Protein kinase B
7 Cisplatin
2 Apigenin (mainly Parsley)
1 Berberine
1 Celecoxib
1 Fisetin
1 Ai-Tong-An-Gao-Ji
1 Garcinol
1 Phenethyl isothiocyanate
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#:4  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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