Aromadendrene oxide 2, induces apoptosis in skin epidermoid cancer cells through ROS mediated mitochondrial pathway
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...
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Published in: | Life sciences (1973) Vol. 197; pp. 19 - 29 |
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Abstract | 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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AbstractList | Aims 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. Material and methods 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. Key findings 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. Significance The results of the present study reveals that AO-(2) a chemical component of essential oils induces apoptosis in A431 and HaCaT cells. AIMSAromadendrene 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.MATERIAL AND METHODSCell 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.KEY FINDINGSAO-(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.SIGNIFICANCEThe results of the present study reveals that AO-(2) a chemical component of essential oils induces apoptosis in A431 and HaCaT cells. 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. [Display omitted] 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. |
Author | Verma, Rama S. Pavithra, P.S. Mehta, Alka |
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Keywords | Aromadendrene oxide 2 Cancer therapy ROS Apoptosis Skin cancer |
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Snippet | Aromadendrene oxide 2 (AO-(2)) is an oxygenated sesquiterpene naturally found as a chemical component of essential oils. In the present study anticancer... Aims Aromadendrene oxide 2 (AO-(2)) is an oxygenated sesquiterpene naturally found as a chemical component of essential oils. In the present study anticancer... AIMSAromadendrene oxide 2 (AO-(2)) is an oxygenated sesquiterpene naturally found as a chemical component of essential oils. In the present study anticancer... |
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SubjectTerms | 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 |
Title | Aromadendrene oxide 2, induces apoptosis in skin epidermoid cancer cells through ROS mediated mitochondrial pathway |
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