Aromadendrene oxide 2, induces apoptosis in skin epidermoid cancer cells through ROS mediated mitochondrial pathway

• Published in: Life sciences (1973) Vol. 197; pp. 19 - 29
• Main Authors: Pavithra, P.S., Mehta, Alka, Verma, Rama S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15-03-2018; Elsevier BV
• Subjects: Annexin V; Anticancer properties; Antitumor activity; Apoptosis; Aromadendrene oxide 2; Ascorbic acid; BAX protein; Bcl-2 protein; Cancer; Cancer therapies; Cancer therapy; Caspase; Caspase-3; Caspase-9; Cell cycle; Cell death; Chemical composition; Cysteine; Cytochrome; Cytochrome c; Cytotoxicity; Essential oils; Flow cytometry; G1 phase; Intracellular; Membrane potential; Mitochondria; Multicellular tumor spheroids; Poly(ADP-ribose) polymerase; Proteins; ROS; Skin; Skin cancer; Spheroids; Aromadendrene oxide 2; Cancer therapy; ROS; Apoptosis; Skin cancer
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2018.01.029

Aromadendrene oxide 2 (AO-(2)) is an oxygenated sesquiterpene naturally found as a chemical component of essential oils. In the present study anticancer activity of AO-(2) has been investigated on A431 human epidermoid cancer and precancerous HaCaT cells.
Cell viability was used to detect cytotoxic activity. Mechanism of cell death induced by AO-(2) treatments was studied using Annexin V-FITC/PI binding, cell cycle analysis, measurement of MMP and ROS generation by flow cytometry. Expression of apoptosis related proteins was investigated by western blot.
AO-(2) inhibited the growth and colony formation ability of A431 and HaCaT cells in concentration dependent manner. It induced cell cycle arrest at G0/G1 phase and apoptosis through intracellular ROS accumulation. Inhibition of intracellular ROS by ascorbic acid and N-acetyl cysteine treatment completely blocked apoptotic effect. N-acetyl cysteine treatment significantly reversed G0/G1 arrest induced by AO-(2). AO-(2) treatment caused loss of mitochondrial membrane potential (ΔΨm), increase in Bax/Bcl-2 ratios, cytochrome c release, activation of caspases (cleaved caspase-3 and caspase-9) and PARP cleavage. AO-(2) also significantly inhibited the growth of multicellular tumor spheroids of A431 and HaCaT cells.
The results of the present study reveals that AO-(2) a chemical component of essential oils induces apoptosis in A431 and HaCaT cells.
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