Breast cancer, effect of cannabinoids in animal models
| Disease model | Treatment | Comparator | Results | Ref. |
|---|---|---|---|---|
| 4 human breast adenocarcinoma cell lines (ER–: HCC1954; TNBC: MDA-MB-231; ER+/PR+ tumour: BT474 and T47D); s.c. xenografts, nude mice, immune-deficient | THC 45 mg/kg, p.o., 3 times a week, for 30 days; Supra-therapeutic doses | THC-E, adjusted to THC 45 mg/kg, p.o., 3 times a week, (extract with 55% THC, 0.3% THCA, 0.4% CBG, CBD (not done); Supra-therapeutic doses | THC < THC-E; In all 4 animal tests pure THC inhibited tumour growth less than THC-E; T47D, THC < THC-E; HCC1954, THC < THC-E; BT474, THC < THC-E; MDA-MB-231, THC < THC-E (triple-negative cancer) | [64] |
| 2 TNBC (murine 4T1.2, and human MVT-1), ortho-topically injected, Balb/C and FVB mice | CBD 10 mg/kg peri-tumoral injection on alternate days for 3 weeks | (vs. control) | CBD slowed down the growth of highly aggressive, TNBC cells (4T1.2) by approximately 25% to 30% (tumour volume and weight). A similar dose-dependent inhibition of cancer growth was also seen after injection of TNBC cells (MVT-1) | [65] |
Murine TNBC breast cancer 4T1; Female BALB/c mice | Lioposomes loaded with CBD (5, 15, or 45 mg/kg) and 15 mg/kg PPD, every 2nd day for 14 days | 20(S)-PPD-liposomes (15 mg/kg of PPD) or CBD-PPD co-loaded liposomes (CP)-liposomes or paclitaxel injection (8 mg/kg), i.v. | Tumour growth inhibition was 46.8% with 15 mg/kg liposomal CBD alone, 50.8% with liposomal PPD alone, 67.4% with CBD-PPD co-loaded liposome (each component 15 mg/kg), 64.4% with paclitaxel (8 mg/kg i.v.); an increase of the CBD component to 45 mg/kg (co-loaded with 15 mg PPD) achieved the highest inhibition (82.2%), a reduction to CBD 5 mg/kg with 15 mg PPD the lowest (46.0%) | [66] |
| Human breast cancer TNBC (MBA-MD-231), s.c. xenografts, athymic mice | CBD 5 mg/kg, twice per week, intra-tumoral injection, 16 days | CBD-rich extract 6.5 mg/kg twice per week, intra-tumoral injection | CBD ≃ CBD-E; Extracts were injected in the tumour in the inoculation region; signif. reduction of the tumour volume after both treatments, with no difference between CBD and CBD-E (~40% lower tumour volume) | [25] |
| Murine TNBC (4T1 cells), s.c. xenograft; BALB/c mice | THC 12.5, 25, or 50 mg/kg, i.p., every other day for 18–21 days | (vs. control) | 25 mg/kg and 50 mg/kg THC led to a signif., dose-dependent increase in tumour mass and metastases, even more pronounced with 50 mg/kg | [67] |
Two TNBC models: 1st, i.v. model: mouse breast cancer (4T1) or human breast cancer cells (MDA-MB231) injected i.v., mouse | CBD 1 mg/kg i.p. daily for approximately 1 month | (vs. control) | CBD increased significantly survival and reduced metastasis up to 75% (EC50: 0.3 mg/kg). Effects on metastasis were dose-dependent (CBD 0.5, 1, or 10 mg/kg i.p, daily | [68] |
| 2nd, orthotopic model: mouse breast cancer cells (4T1) were injected into mammary glands | CBD 1 mg/kg i.p. per day, for approximately 1 month | (vs. control) | CBD reduced metastasis even when administered only three times per week. CBD did, however, not inhibit primary tumour growth | [68] |
| Xeno-transplanted TNBC (MDA-MB-231 cells s.c.), female nude mice | CBD 10 mg/kg, i.p., twice weekly, for 2 weeks | vs. control; vs. CBD-EV (EV loaded with CBD 5 mg/kg) vs. DOX 2 mg/kg, vs. CBD 5 mg/kg one day before DOX, vs. CBD-EV 5 mg/kg one day before DOX | After 2 weeks the tumour volumes were (estimated): Control 8,200 mm3; EVs 7,500 mm3; CBD 10 mg/kg 6,800 mm3; CBD-EV 5 mg/kg 7,000 mm3; DOX 2 mg/kg 4,200 mm3; CBD 5 mg/kg with DOX 1 day later 4,000 mm3; CBD-EV with DOX 1 day later 3,500 mm3; CBD before doxorubicin sensitized tumour cells | [69] |
CBD-E: CBD-extract (synonym: CBD-BDS, CBD botanical drug substance); PPD: protopanaxadiol; DOX: doxorubicin; EVs: extracellular vesicles; p.o.: per os; i.v.: intravenous injection; signif.: significant; ≃: almost equal; ~: about
