Cisplatin / Casp3 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)


Casp3, CPP32, Cysteinyl aspartate specific proteinase-3: Click to Expand ⟱
Source:
Type:
Also known as CP32.
Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death.
As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression.
Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent.
On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer.
Procaspase-3 is a apoptotic marker protein.
Prognostic significance:
• High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers.
• Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.


Scientific Papers found: Click to Expand⟱
1295- AG,  Cisplatin,    Chemosensitizing Effect of Astragalus Polysaccharides on Nasopharyngeal Carcinoma Cells by Inducing Apoptosis and Modulating Expression of Bax/Bcl-2 Ratio and Caspases
- in-vivo, Laryn, NA
AntiTum↑, Apoptosis↑, Bcl-2↓, BAX↑, Casp3↑, Casp9↑, Bax:Bcl2↑,
584- Api,  Cisplatin,    Apigenin potentiates the antitumor activity of 5-FU on solid Ehrlich carcinoma: Crosstalk between apoptotic and JNK-mediated autophagic cell death platforms
- in-vivo, Var, NA
Beclin-1↑, Casp3↑, Casp9↑, JNK↑, Mcl-1↓, Ki-67↓,
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↑,
5919- Cats,  Cisplatin,    Uncaria tomentosa Leaves Decoction Modulates Differently ROS Production in Cancer and Normal Cells, and Effects Cisplatin Cytotoxicity
- in-vitro, Liver, HepG2
ROS↑, GSH↓, Apoptosis↑, Casp3↑, Casp7↑, NF-kB↓, selectivity↑, ChemoSen↑, chemoP↑,
444- CUR,  Cisplatin,    LncRNA KCNQ1OT1 is a key factor in the reversal effect of curcumin on cisplatin resistance in the colorectal cancer cells
- vitro+vivo, CRC, HCT8
TumVol↓, Apoptosis↑, Bcl-2↓, Cyt‑c↑, BAX↑, cl‑Casp3↑, cl‑PARP1↑, miR-497↑, KCNQ1OT1↓,
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↓,
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↓,
1064- LT,  Cisplatin,    Inhibition of cell survival, invasion, tumor growth and histone deacetylase activity by the dietary flavonoid luteolin in human epithelioid cancer cells
- vitro+vivo, Lung, LNM35 - in-vitro, CRC, HT-29 - in-vitro, Liver, HepG2 - in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Casp3↑, Casp7↑, HDAC↓,
5183- PEITC,  Cisplatin,    Phenethyl Isothiocyanate Induces Apoptosis Through ROS Generation and Caspase-3 Activation in Cervical Cancer Cells
- in-vitro, Cerv, HeLa - in-vitro, Nor, HaCaT
DNAdam↑, Apoptosis↑, ChemoSen↑, ROS↑, mt-ROS↑, Casp↑, Casp3↑, selectivity↑, TumCP↓, tumCV↓, eff↓,

Showing Research Papers: 1 to 9 of 9

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

GSH↓, 1,   ROS↑, 4,   mt-ROS↑, 1,  

Mitochondria & Bioenergetics

MMP↓, 1,  

Core Metabolism/Glycolysis

Histones↑, 1,   PI3K/Akt↓, 1,  

Cell Death

p‑Akt↓, 1,   Apoptosis↑, 5,   BAX↑, 4,   Bax:Bcl2↑, 1,   Bcl-2↓, 3,   Casp↑, 1,   Casp3↑, 7,   cl‑Casp3↑, 2,   Casp7↑, 3,   Casp9↑, 4,   Cyt‑c↑, 1,   JNK↑, 1,   Mcl-1↓, 1,   miR-497↑, 1,  

Transcription & Epigenetics

HATs↓, 1,   KCNQ1OT1↓, 1,   tumCV↓, 3,  

Autophagy & Lysosomes

Beclin-1↑, 1,  

DNA Damage & Repair

ATM↑, 1,   ATR↑, 1,   DNAdam↑, 2,   P53↑, 1,   cl‑PARP↑, 1,   cl‑PARP1↑, 1,  

Cell Cycle & Senescence

TumCCA↑, 2,  

Proliferation, Differentiation & Cell State

ERK↓, 1,   HDAC↓, 1,   Let-7↑, 1,   NOTCH1↓, 1,   p‑PI3K↓, 1,   STAT3↓, 1,   Wnt/(β-catenin)↓, 1,  

Migration

E-cadherin↑, 1,   Ki-67↓, 1,   MMP9↓, 1,   TGF-β↓, 1,   TumCP↓, 1,   Vim↓, 1,   Zeb1↓, 1,   ZEB2↓, 1,  

Angiogenesis & Vasculature

VEGF↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,   IL6↓, 1,   NF-kB↓, 3,  

Drug Metabolism & Resistance

ChemoSen↑, 4,   eff↓, 2,   selectivity↑, 2,  

Clinical Biomarkers

IL6↓, 1,   Ki-67↓, 1,  

Functional Outcomes

AntiTum↑, 1,   chemoP↑, 1,   TumVol↓, 1,  
Total Targets: 58

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
9 Cisplatin
2 Garcinol
1 Astragalus
1 Apigenin (mainly Parsley)
1 borneol
1 Cat’s Claw
1 Curcumin
1 Paclitaxel
1 Luteolin
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#:42  State#:%  Dir#:2
wNotes=0 sortOrder:rid,rpid

 

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