Table 8.
Anticancer effects of Carnosic Acid (CA). In vitro studies: breast, pancreatic, prostate and ovarian cancer.
| Cell Type | Dose/Duration | Findings | Mechanism | Reference |
|---|---|---|---|---|
| MCF-7 (ER+) (Breast adenocarcinoma), MDA-MB-231 (Breast adenocarcinoma) | 6.25–50 µg/mL (18.8–150 µM) CA (48 h) | ↓ cell viability | [30] | |
| MCF-7 (Breast adenocarcinoma), MDA-MB-468 (Breast adenocarcinoma) | 0.5–40 µg/mL (1.5–120 µM) CA (6–96 h) | ↓ proliferation ↑ apoptosis ↑ cell cycle arrest IC50: 3µg/mL (9 µM) (88 h) |
↑ CYP4F3, GCLC, SLC7A11, CDKN1A expression | [54] |
| MDA-MB-361 (Breast adenocarcinoma) | 20–60 µM CA (24 h) | ↑ apoptosis | [55] | |
| MDA-MB-361 (Breast adenocarcinoma) | 20 µM CA (24 h) | ↓ proliferation ↑ apoptosis |
↑ TRAIL-mediated apoptosis ↓ c-FLIP, Bcl-2 ↑ DR5, Bim, PUMA, CHOP |
[56] |
| RINm5F (Insulinoma) | 12–100 µg/mL (36.1–300 µM) CA (24–48 h) | ↓ cell viability | [27] | |
| MIA-PaCa-2 (Pancreatic carcinoma), PANC-1 (Pancreatic carcinoma) | 2–18 µg/mL (6.02–54.15 µM) CA (48 h) | ↓ cell viability | [21] | |
| DU145 (Prostate carcinoma), PC3 (Prostate adenocarcinoma) | 6.25–50 µg/mL (18.8–150 µM) CA (48h) | ↓ cell viability | [30] | |
| PC3 (Prostate adenocarcinoma) | 20–100 µM CA (0–72 h) | ↓ proliferation ↑ apoptosis |
↓ casp 8, casp 9, Bcl-2, Bid, IAP, p-Akt, p-GSK3, NF-κB ↑ casp 3, casp 7, PARP cleavage, Bax, cyt c, PP2A |
[58] |
| LNCaP (Prostate carcinoma), PC3 (Prostate adenocarcinoma), DU-145 (Prostate carcinoma) | 10 µM CA (72 h) | ↓ proliferation | ↓ EpRE/ARE transcription system ↓ PSA secretion |
[57] |
| A2780 (Ovarian carcinoma), A2780CP70 (cisplatin-resistant) (Ovarian carcinoma) | 2.5–10 µg/mL (7.2–30 µM) CA (48 h) | ↓ cell proliferation Enhanced sensitivity of cisplatin-resistant cells |
[34] |
CYP4F3 (leukotriene-B(4)omega-hydroxylase 2), GCLC (glutamate-cysteine ligase catalytic subunit), SLC7A11 (solute carrier family 7 member 11), CDKN1A (cyclin-dependent kinase inhibitor 1A), TRAIL (TNF-related apoptosis-inducing ligand), c-FLIP (cellular FLICE (FADD-like-IL-1β-converting enzyme)-inhibiting protein), DR5 (death receptor 5), Bim (Bcl-2-like protein 11), PUMA (p53 upregulated modulator of apoptosis), CHOP (C/EBP homologous protein), casp (caspase), Bcl-2 (B-cell CLL/lymphoma 2), Bid (BH3 interacting-domain), IAP (inhibitor of apoptosis), p-Akt (phosphorylated protein kinase B), p-GSK3 (phosphorylated glycogen synthase kinase 3), NF-κB (nuclear factor kappa B), PARP (poly (ADP-ribose) polymerase), Bax (Bcl-2-like protein 4), cyt c (cytochrome c), PP2A (protein phosphatase 2A), EpRE (electrophile responsive element), ARE (antioxidant response element), PSA (prostate specific antigen).