Lasiodin / Cyt‑c Cancer Research Results

Las, Lasiodin: Click to Expand ⟱
Features:

Lasiodin — also reported as lasiokaurin (LAS; CAS 28957-08-6), is a naturally occurring oxygenated ent-kaurane diterpenoid with the molecular formula C22H30O7 and molecular weight ~406.5 Da. It is an experimental plant-derived anticancer compound isolated from species of the genus Isodon, including Isodon serra (syn. Rabdosia serra) and Isodon rubescens. Lasiodin is not an approved anticancer drug and remains a preclinical research compound. Recent studies substantially expand its known activity beyond the original nasopharyngeal-carcinoma work, demonstrating effects in breast cancer and hepatocellular carcinoma models.

Primary mechanisms (ranked):

  1. Disruption of prosurvival PI3K/PDPK1/AKT/mTOR signaling, contributing to growth inhibition, metabolic stress, altered autophagic flux and apoptosis.
  2. Induction of mitochondrial apoptosis through Apaf-1, cytochrome-c release, caspase-9/caspase-3 activation and PARP cleavage.
  3. PLK1 suppression with downstream CDC25C inhibition, producing G2/M cell-cycle arrest and apoptosis.
  4. STAT3 suppression, including PI3K/AKT-associated STAT3 inhibition in breast cancer and JAK2/STAT3 suppression in hepatocellular carcinoma.
  5. Autophagic-flux disruption; effects appear context-dependent, including impaired autophagosome degradation/lysosomal function in breast cancer and inhibition of autophagy initiation plus disruption of SNARE-mediated autophagosome-lysosome fusion in hepatocellular carcinoma.
  6. Suppression of COX-2/NF-κB signaling, including reduced NF-κB promoter binding and nuclear localization.
  7. Suppression of AKT/MAPK signaling, including reduced phosphorylation of ERK1/2, p38 and JNK in nasopharyngeal carcinoma.
  8. Suppression of glycolytic ATP production and cellular energy homeostasis, producing metabolic stress in breast cancer cells.
  9. Suppression of migration, invasion and metastatic phenotypes in several cancer models.

Bioavailability / PK relevance: Human pharmacokinetic parameters, oral bioavailability, plasma half-life, metabolic pathways and clinically achievable systemic concentrations have not been adequately established for purified lasiodin/lasiokaurin. Consequently, translation of the low-micromolar concentrations used experimentally to a feasible human dose remains unknown. No validated clinical formulation or established therapeutic dose is available.

In-vitro vs systemic exposure relevance: Anticancer activity is commonly reported at approximately 1–10 µM in cultured cancer cells, including breast, nasopharyngeal and hepatocellular carcinoma models. There are presently insufficient human PK data to establish whether these concentrations are achievable or sustainable systemically. Selectivity is incomplete: normal MCF-10A breast cells were less sensitive at 24 hours but became substantially more sensitive with prolonged exposure, indicating that cytotoxicity is not necessarily cancer-specific.

Clinical evidence status: Preclinical. Evidence includes multiple cancer-cell studies, patient-derived breast-cancer organoids and mouse xenograft models, including breast cancer and hepatocellular carcinoma. Lasiodin/lasiokaurin has also enhanced sorafenib activity in preclinical hepatocellular carcinoma models. No established human anticancer trials, approved indication or validated adjunct-use regimen was identified.

Lasiodin Mechanistic Profile

Rank Pathway / Axis Cancer Cells Normal Cells Primary Effect Notes / Interpretation
1 PI3K PDPK1 AKT mTOR ↓ Not established Growth inhibition, metabolic stress, apoptosis and autophagic-flux disruption Strongly supported across recent breast-cancer studies. Reduced AKT/mTOR signaling is a recurring central mechanism.
2 Mitochondrial Apaf-1 cytochrome c caspase apoptosis ↑ Not established Intrinsic apoptotic cell death ↑ Apaf-1 and cytochrome-c release with ↑ caspase-9, caspase-3 and PARP cleavage. Supported initially in nasopharyngeal carcinoma and consistent with apoptosis observed in newer models.
3 PLK1 CDC25C cell-cycle control ↓ Not established G2/M arrest and apoptosis LAS ↓ PLK1 mRNA/protein, ↓ CDC25C and ↓ AKT phosphorylation in breast cancer. Antitumor activity was reproduced in organoid and xenograft models.
4 STAT3 signaling ↓ Not established Reduced proliferation and increased apoptosis STAT3 inhibition is supported in breast cancer; recent HCC work additionally identifies ↓ JAK2/STAT3 signaling.
5 Autophagic flux ↓ functional flux (context-dependent) Not established Loss of protective nutrient recycling and increased cancer-cell stress Mechanistically complex. Breast-cancer studies report ↑ initiation but ↓ autophagosome degradation through PDPK1-AKT/mTOR-dependent lysosomal impairment. HCC studies report ↓ initiation plus impaired SNARE-mediated autophagosome-lysosome fusion.
6 SNARE autophagosome lysosome fusion ↓ Not established Blocks completion of autophagy Recent HCC evidence indicates disruption of mTOR-regulated SNARE-complex formation, contributing to sensitization to sorafenib.
7 COX-2 NF-κB ↓ Not established Reduced survival, proliferation and inflammatory signaling ↓ COX-2 expression and ↓ NF-κB binding to the COX-2 promoter; p65 redistribution from nucleus to cytoplasm was observed in NPC cells.
8 AKT MAPK ERK p38 JNK ↓ Not established Reduced proliferation and survival signaling Lasiodin ↓ phosphorylation of AKT, ERK1/2, p38 and JNK in nasopharyngeal carcinoma. Pharmacologic inhibitor experiments support functional involvement of these pathways.
9 Glycolysis and ATP production ↓ Not established Energy depletion and metabolic stress Recent breast-cancer evidence shows impaired glycolytic ATP production accompanying blockade of autophagic nutrient recycling.
10 DNA integrity and PARP ↓ repair capacity / ↑ DNA damage Not established DNA damage and apoptosis Breast-cancer models show reduced PARP and evidence of DNA damage, particularly at cytotoxic LAS concentrations.
11 Migration and invasion ↓ Not established Reduced metastatic phenotype Migration and invasion are inhibited in nasopharyngeal and breast-cancer models.
12 G2/M cell-cycle progression ↓ Not established Cell-cycle arrest Observed in breast-cancer and HCC models and linked particularly to PLK1/CDC25C suppression.
13 Sorafenib resistance and chemosensitization ↑ sorafenib sensitivity Not established Chemosensitization LAS suppresses sorafenib-induced protective autophagy and increases sorafenib efficacy in HCC cells and xenografts.
14 Normal-cell cytotoxicity ↓ cancer-cell viability ↓ viability (dose-dependent) (time-dependent) Limits therapeutic selectivity MCF-10A normal breast cells were substantially less sensitive than cancer cells at 24 h, but the selectivity margin narrowed markedly at 48–72 h.
15 Clinical Translation Constraint Preclinical activity Human safety unknown Major translational limitation No established human PK, bioavailability, chronic toxicology, therapeutic dose or clinical efficacy. Low-micromolar in-vitro activity cannot presently be assumed achievable in humans.


Cyt‑c, cyt-c Release into Cytosol: Click to Expand ⟱
Source:
Type:
Cytochrome c
** The term "release of cytochrome c" ** an increase in level for the cytosol.
Small hemeprotein found loosely associated with the inner membrane of the mitochondrion where it plays a critical role in cellular respiration. Cytochrome c is highly water-soluble, unlike other cytochromes. It is capable of undergoing oxidation and reduction as its iron atom converts between the ferrous and ferric forms, but does not bind oxygen. It also plays a major role in cell apoptosis.

The term "release of cytochrome c" refers to a critical step in the process of programmed cell death, also known as apoptosis.
In its new location—the cytosol—cytochrome c participates in the apoptotic signaling pathway by helping to form the apoptosome, which activates caspases that execute cell death.
Cytochrome c is a small protein normally located in the mitochondrial intermembrane space. Its primary role in healthy cells is to participate in the electron transport chain, a process that helps produce energy (ATP) through oxidative phosphorylation.
Mitochondrial outer membrane permeability leads to the release of cytochrome c from the mitochondria into the cytosol.
The release of cytochrome c is a pivotal event in apoptosis where cytochrome c moves from the mitochondria to the cytosol, initiating a chain reaction that leads to programmed cell death.

On the one hand, cytochrome c can promote cancer cell survival and proliferation by regulating the activity of various signaling pathways, such as the PI3K/AKT pathway. This can lead to increased cell growth and resistance to apoptosis, which are hallmarks of cancer.
On the other hand, cytochrome c can also induce apoptosis in cancer cells by interacting with other proteins, such as Apaf-1 and caspase-9. This can lead to the activation of the intrinsic apoptotic pathway, which can result in the death of cancer cells.
Overexpressed in Breast, Lung, Colon, and Prostrate.
Underexpressed in Ovarian, and Pancreatic.
Scientific Papers found: Click to Expand⟱
8175- Las,    Lasiodin Inhibits Proliferation of Human Nasopharyngeal Carcinoma Cells by Simultaneous Modulation of the Apaf-1/Caspase, AKT/MAPK and COX-2/NF-κB Signaling Pathways
- in-vitro, NPC, NA
tumCV↓, TumCMig↓, APAF1↑, Cyt‑c↑, cl‑PARP↑, cl‑Casp3↑, cl‑Casp9↑, Apoptosis↑, p‑Akt↓, p‑ERK↓, p‑p38↓, p‑JNK↓, COX2/PTGS2↓, NF-kB↓, chemoPv↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Cell Death(tgid=5) ⓘ

p‑Akt↓, 1,   APAF1↑, 1,   Apoptosis↑, 1,   cl‑Casp3↑, 1,   cl‑Casp9↑, 1,   Cyt‑c↑, 1,   p‑JNK↓, 1,   p‑p38↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

tumCV↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

cl‑PARP↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

p‑ERK↓, 1,  

Migration(tgid=13) ⓘ

TumCMig↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   NF-kB↓, 1,  

Functional Outcomes(tgid=23) ⓘ

chemoPv↑, 1,  
Total Targets: 15

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Cyt‑c, cyt-c Release into Cytosol
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#:113  Target#:77  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page