Hallmarks of Cancer Apigenin Targeted by Apigenin.

1. Sustaining Proliferative Signaling

• Colorectal cancer:
  Apigenin inhibits proliferation through G2/M cell cycle arrest.
• Breast cancer:
  Apigenin induces G2/M arrest and p21WAF1/CIP1 expression.
• Prostate cancer:
  Apigenin inhibits cell cycle progression and induces G0/G1 arrest.

2. Evading Growth Suppressors

• Lung cancer:
  Apigenin increases the expression of p53-regulated genes like DR4 and DR5.
• Prostate cancer:
  Apigenin increases p53 expression along with other apoptotic markers.

3. Resisting Cell Death

Multiple cancer types: 

Apigenin induces apoptosis through various mechanisms, including:

• Activation of caspases
• Increased Bax/Bcl-2 ratio
• Cytochrome c release
• PARP cleavage

4. Enabling Replicative Immortality

Neuroblastoma: 

Apigenin treatment inhibits hTERT expression.

5. Inducing Angiogenesis

Multiple cancer types: 

Apigenin inhibits VEGF expression and angiogenesis.

6. Activating Invasion and Metastasis

Breast cancer: 

Apigenin inhibits epithelial-mesenchymal transition (EMT).

Prostate cancer: 

Apigenin reduces the invasion and migration of cancer stem cells.

Cancer Stem Cell Signaling Pathways Affected:

Wnt/β-catenin Pathway

Colorectal cancer: Apigenin suppresses this pathway.

Hippo-YAP/TAZ Pathway

Triple-negative breast cancer: Apigenin inhibits YAP/TAZ activity.

PI3K/AKT/mTOR Pathway

Prostate cancer: Apigenin reduces CD44+ stem cell survival through this pathway.

Ovarian cancer: Apigenin inhibits self-renewal capacity by inactivating CK2α.

Hedgehog/Gli Signaling

Lung cancer: Apigenin down-regulates this pathway.

NF-κB Pathway

Prostate cancer: Apigenin reduces CD44+ stem cell survival through this pathway.

STAT3 Signaling

Melanoma: Apigenin inhibits STAT3 signaling.

These effects of apigenin on cancer hallmarks and stem cell signalling pathways in pre-clinical research demonstrate its potential as a multi-targeted anticancer agent across various types of cancer.

Learn more: Naponelli V, Rocchetti MT, Mangieri D. Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading. International Journal of Molecular Sciences. 2024; 25(10):5569. https://doi.org/10.3390/ijms25105569

When I was targeting cancer stem cells and blocking all the pathways I could with everything I could get my hands on back in 2018-19, I was drinking loads of organic chamomile tea and parsley tea, and a liposomal apigenin supplement just did not exist.

Dried parsley has been reported to have the maximum quantity of apigenin at 45,035 μg/g. Additional sources of Apigenin are dried flower of chamomile, containing 3,000 to 5,000 μg/g; celery seeds, containing 786.5 μg/g; and vine spinach and Chinese celery, containing 622 μg/g and 240.2 μg/g. I'm still drinking my chamomile tea and eating parsley out of the garden daily. I am super grateful that MCS formulas have created a Liposomal Apigenin containing a whopping  200 mg Apigenin extracted from Grapefruit Peel and encapsulated in liposomes to ensure it reaches the cells. It just makes dosing easy.

Dosing notes: 1 x 200 mg liposomal delivered dose could reach the 1–5μmol/L blood concentration required for action.

We can also consider taking a weekend break from the capsules if we are concerned about a potential accumulation. Read more here

Toxicity research and liver protection induced by Apigenin

It looks like there is one study out there suggesting high dose Apigenin might be toxic to the liver. The study was done using IV Apigenin on mice and it's the only one, where as there are are several examples of research pointing to  Apigenin being protective against liver injury. Here are a few:

• Antioxidative and Protective Actions of Apigenin in a Paracetamol-Induced Hepatotoxicity Rat Model
• Apigenin Prevents Acetaminophen-Induced Liver Injury by Activating the SIRT1 Pathway
• Protective effects of apigenin on altered lipid peroxidation, inflammation, and antioxidant factors in methotrexate-induced hepatotoxicity
• Apigenin Alleviates Liver Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Autophagy via TGF-β1/Smad3 and p38/PPARα Pathways 

So, overall, the literature reports in favour of liver protection induced by apigenin and not toxicity. Furthermore, a review on apigenin referring to doses used in animals even higher, with no toxicity on the exposed areas is here Based on the literature referenced above:

• Apigenin is helpful to the liver.
• The dose of Apigenin in one 200mg capsule of MCS Formulas Liposomal Apigenin provides an Apigenin blood level below the dose reported by the one acute IV Apigenin mouse study that points to  potentially presenting toxicity.