Article by Justin L Scharton, Independent Researcher
Article written on April 4, 2025
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Disclaimer: This information is provided for informational purposes only and is not intended to diagnose, treat, or cure any condition. Always consult a licensed medical professional before making changes to your healthcare regimen.
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A Deeper Look at Lung Cancer: Subtypes, Receptors, and Innovations
There are different subtypes of lung cancer. Most available research is centered around the A549 subtype of non-small cell lung cancer (NSCLC), and Lewis Lung Cancer (LLC).
Non-Small Cell Lung Cancer (NSCLC) subtype Lung adenocarcinoma (A549)
Receptors involved
CB1, CB2, TRPV1, TRPV3, TRPV4, TRPM7.
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Cannabinoids for NSCLC
Combining CBD, CBN, THC, and THCV will affect all receptors involved, and they are easy to get.
Most cannabinoids will help, and they are categorized below by each receptor
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Terpenes for NSCLC
Humulene, b-caryophyllene, carvacrol. Possibly b-myrcene, (-)-α-bisabolol, nerolidol, geraniol, and cedrol.
More details on each are described below.
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TRPV1
Terpenes that interact with the TRPV1 receptor
b-myrcene, (-)-α-bisabolol is a TRPV1 antagonist, nerolidol is a TRPV1 agonist, geraniol is a TRPV1 putative modulator, and cedrol is a TRPV1 modulator. (68C, 52D, 81D 3E)
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TRPV1 agonists
Capsaicin, CBC, CBG, CBD, CBN, CBDA, CBGA, CBGV, CBDV, THCV, THCVA (3A, 13A 19A,20A,21A)
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TRPV1 acts as a tumor promoter in NSCLC through IGF1R signaling and regulating GABA release to affect the tumor immune response. TRPV1 inhibition suppressed NSCLC proliferation. (97F)
It does seem that TRPV1 agonists are risky for lung cancer cells with overexpressed TRPV1, and activating that receptor could promote growth signals. However, TRPV1 agonists can also desensitize and downregulate the receptor over time. Research indicates that TRPV1 agonists cause long-term receptor downregulation by endocytosis and degradation of the channel, (79E) which could ultimately reduce the pro-tumor effects of TRPV1 overexpression.
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TRPV3
TRPV3 agonists
CBD, CBGA, CBGV, THCV, camphor, menthol, dihydrocarveol, eucalyptol (1,8-cineole), carvacrol, thymol, carveol, (+)-borneol, eugenol. (3A,19A, 36A, 38A, 39A)
TRPV3 was overexpressed in NSCLC and correlated with lung cancer progression. TRPV3 activation could promote proliferation of lung cancer cells. (98F)
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TRPV4
TRPV4 agonists include
CBDV, CBG, THCV, CBN, CBGV, CBGA (3A,54A)
TRPV4 induces cell death, inhibits cell proliferation and migration A549 breast cancer. This study was specific about increasing the expression of TRPV4 was needed to activate the p38 MAPK signal pathway, inducing cell death. TRPV4 agonists need to be researched for this activity, as it could have the same effect. (99F)
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TRPM7
TRPM7 ligand
Carvacrol (found in Oregano) is a TRPM7 inhibitor. (16E,18E)
TRPM7 is overexpressed in lung cancer cell lines SPCA-1, NCI-H520, SK-MES-1, A549 and 95D. Inhibiting TRPM7 stopped the epithelial-to-mesenchymal transition (EMT), and suppressed stemness markers and phenotypes, and the Hsp90α/uPA/MMP2 axis. (1G)
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CB1 and CB2
CB1 ligands
humulene, THC, Anandamide (AEA), THCV (antagonist), CBG (partial agonist), CBN (Weak agonist). (6D 69A 70A 71A)
CB2 ligands
b-caryophyllene, CBD (Inverse agonist), CBC (agonist) CBG (partial agonist), THCV (Partial agonist). (69A 70A 72A 73A)
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Activating CB1 or CB2 can reduce tumor cell invasiveness. (2G)
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Lewis Lung Cancer (LLC)
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Receptors involved
TRPA1, TRPM8 (3G)
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TRPA1 agonists
CBC, CBD, CBG, CBN, THC, CBDV, THCV, CBGV, THCA, CBDA, CBGA, THCVA. (2A,3A,4A)
TRPM8 antagonists
CBC, CBD, CBG, CBN, THC, THCA, THCV, CBDA, CBDV, CBGA, CBGV, THCVA (3A,19A,54A)
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Possible terpene to avoid
Eucalyptol (1,8 Cineole) is a TRPM8 agonist.(33D) Eucalyptol is known for having anti-cancer benefits to some cancers, but for lung cancer types that are worsened by the activation of TRPM8, it is not known if eucalyptol will do the same. That would need to be researched.
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Lewis Lung Cancer Subtypes
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LLC-1
TRPM8 is 3 times more abundant than TRPA1. (3G)
In a cold environment (where TRPM8 becomes activated), autophagy is less effective, which supports tumor progression. (3G)
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LLC-2
Has equal amounts of TRPM8 and TRPA1. (3G)
Displays greater adhesion, migration, and invasiveness than LLC‑1 and LLC‑3. (3G)
More resistant to low-temperature conditions (hypothermia), showing reduced autophagy changes even when TRPM8 is activated by cold. (3G)
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LLC-3
TRPA1 is three times more abundant than TRPM8. (3G)
Shows lower invasiveness than LLC‑2 but in some tests is more invasive than LLC‑1. (3G)
Under hypothermia, LLC‑3 undergoes more pronounced autophagy compared to both LLC‑1 and LLC‑2. (3G)
Sources
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