Cannabinoid Combination Induces Cytoplasmic Vacuolation in MCF-7 Breast Cancer Cells.
Recardia SchoemanNatasha BeukesCarminita Lara FrostPublished in: Molecules (Basel, Switzerland) (2020)
This study evaluated the synergistic anti-cancer potential of cannabinoid combinations across the MDA-MB-231 and MCF-7 human breast cancer cell lines. Cannabinoids were combined and their synergistic interactions were evaluated using median effect analysis. The most promising cannabinoid combination (C6) consisted of tetrahydrocannabinol, cannabigerol (CBG), cannabinol (CBN), and cannabidiol (CBD), and displayed favorable dose reduction indices and limited cytotoxicity against the non-cancerous breast cell line, MCF-10A. C6 exerted its effects in the MCF-7 cell line by inducing cell cycle arrest in the G2 phase, followed by the induction of apoptosis. Morphological observations indicated the induction of cytoplasmic vacuolation, with further investigation suggesting that the vacuole membrane was derived from the endoplasmic reticulum. In addition, lipid accumulation, increased lysosome size, and significant increases in the endoplasmic reticulum chaperone protein glucose-regulated protein 78 (GRP78) expression were also observed. The selectivity and ability of cannabinoids to halt cancer cell proliferation via pathways resembling apoptosis, autophagy, and paraptosis shows promise for cannabinoid use in standardized breast cancer treatment.
Keyphrases
- breast cancer cells
- endoplasmic reticulum
- cell cycle arrest
- cell death
- pi k akt
- endoplasmic reticulum stress
- cell proliferation
- oxidative stress
- signaling pathway
- protein protein
- binding protein
- cancer therapy
- papillary thyroid
- endothelial cells
- amino acid
- poor prognosis
- transcription factor
- induced pluripotent stem cells
- cell cycle
- long non coding rna
- type diabetes
- lymph node metastasis
- metabolic syndrome
- blood glucose
- squamous cell carcinoma
- insulin resistance
- squamous cell
- childhood cancer
- single molecule
- heat shock
- skeletal muscle