cytochrome-c-t and carvacrol

Carvacrol is a monoterpenic phenol found in essential oils, is considered a safe food additive, and possesses various therapeutic properties. Numerous studies have also deciphered the protective role of carvacrol on various cytotoxicities. We clarify the effects of carvacrol on cadmium-induced apoptosis in PC12 cells. Carvacrol while co-exposed with cadmium for 48 h raised PC12 cell viability in comparison to only cadmium exposed group. The co-exposure increased the cellular glutathione levels and promoted the expression of glutathione reductase. The magnitude of DNA fragmentation caused by cadmium was also ameliorated by carvacrol. Flow cytometry exhibited the apoptosis rate augmented by cadmium was reduced by carvacrol. Western blotting revealed that cadmium and carvacrol co-exposure alleviated the cadmium-induced down-regulations of mammalian target of rapamycin (mTOR), protein kinase B (Akt), nuclear factor kappa-light-chain-enhancer of activated B cells (NFКB), extracellular signal-regulated kinase-1 (ERK-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) expressions. The co-exposure also reversed action of cadmium by suppressing the cleavage of caspase 3 and reducing the cytosolic levels of cytochrome c and apoptosis inducing factor (AIF). Moreover, carvacrol upon co-exposure significantly increased the intracellular metallothionein content. In conclusion, carvacrol strongly reduced cadmium-triggered oxidative stress and caspase-dependent and caspase-independent apoptosis in PC12 cells.

Topics: Animals; Apoptosis; Apoptosis Inducing Factor; Cadmium; Caspase 3; Cell Survival; Cymenes; Cytochromes c; DNA Damage; Glutathione; Glutathione Reductase; L-Lactate Dehydrogenase; Oxidative Stress; PC12 Cells; Rats

Although the anti-tumor effects of carvacrol have been demonstrated earlier, the exact underlying molecular mechanisms involved in its action have not been defined and in the present study an attempt has been made to identify the mechanism of carvacrol induced cell death in human metastatic breast cancer cells, MDA-MB 231.. Apoptosis induced by carvacrol was determined based on different assays like MTT assay, Annexin V, mitochondrial membrane potential assay, multicaspase activation assay and cell cycle analysis by flow cytometer. Cleavage of PARP, cytochrome c release and modulation of Bax and Bcl2 ratio by Western blot analysis were also studied.. The study clearly showed induction of apoptosis by carvacrol in MDA-MB 231 cells dose dependently at an IC(50) of 100 microM with a decrease in the mitochondrial membrane potential of the cells resulting in release of cytochrome c from mitochondria, caspase activation and cleavage of PARP.. The data in the present study clearly demonstrated anti-tumor effects of carvacrol on human metastatic breast cancer cells, MDA-MB 231, and that the compound could have a potential therapeutic significance in treating cancer.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Caspases; Cell Line, Tumor; Cell Proliferation; Cymenes; Cytochromes c; Dose-Response Relationship, Drug; Female; Humans; Inhibitory Concentration 50; Membrane Potential, Mitochondrial; Mitochondria; Monoterpenes; Origanum; Phytotherapy; Plant Extracts; Poly(ADP-ribose) Polymerases; Thymus Plant