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1.
Int J Pharm ; 578: 119100, 2020 Mar 30.
Article in English | MEDLINE | ID: mdl-32014600

ABSTRACT

Squamous cell carcinoma treatment has limited therapeutic options and the incidence rate is increasing recently. In the present investigation, we developed poly(lactic-co-glycolic acid) (PLGA) nanopatterned films (NPFs) through poly dimethyl siloxane (PDMS) cast molding technique and explored its therapeutic efficacy in combination with curcumin and tocopherol poly (ethylene glycol) 1000 succinate (TPGS). Herein, we demonstrate the preparation and characterization of curcumin loaded tocopherol polyethylene glycol 1000 succinate stabilized poly (lactic-co-glycolic) acid nanopatterned films (CTP-NPFs). CTP-NPFs showed good in vitro cytotoxicity towards human skin cancer cell line (A431) when compared to that of unpattern films. CTP-NPFs effectively inhibited the progression of 7, 12-Dimethylbenz[a]anthracene (DMBA)/croton oil induced skin cancer in Swiss albino mice. The nanopatterned films could be used as an alternate treatment for skin cancer.


Subject(s)
Curcumin/chemistry , Curcumin/pharmacology , Nanoparticles/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Skin Neoplasms/drug therapy , Vitamin E/chemistry , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Carcinoma, Squamous Cell/drug therapy , Cell Line, Tumor , Drug Liberation , Humans , Mice , Particle Size , Polyethylene Glycols/chemistry
2.
Drug Discov Today ; 24(2): 644-655, 2019 02.
Article in English | MEDLINE | ID: mdl-30508640

ABSTRACT

The increasing incidence of cutaneous malignancies signifies the need for multiple treatment options. Several available reviews have emphasized the potential role of various botanical extracts and naturally occurring compounds as anti-skin-cancer agents. Few studies relate to the role of chemoprevention and therapeutic activity of essential oils (EOs) and EO components. The present review summarizes an overview of chemopreventive, anti-melanoma and anti-nonmelanoma activities of EOs from various plants and EO components in in vitro and in vivo models with special emphasis on skin cancer. Also, the mechanisms by which EOs and EO components exert their effects to induce cell death are presented.


Subject(s)
Melanoma/drug therapy , Melanoma/prevention & control , Oils, Volatile/therapeutic use , Skin Neoplasms/drug therapy , Skin Neoplasms/prevention & control , Animals , Humans , Skin/drug effects
3.
Phytomedicine ; 50: 184-195, 2018 Nov 15.
Article in English | MEDLINE | ID: mdl-30466977

ABSTRACT

BACKGROUND: The genus Pamburus (Rutaceae) comprises the only species, Pamburus missionis (Wight) Swingle. Pamburus missionis is traditionally used in the treatment of swellings, chronic rheumatism, paralysis and puerperal diseases. PURPOSE: The present study investigates the cancer chemotherapeutic potential of essential oil (EO) from P. missionis. METHODS: EO was isolated by steam distillation and chemical composition was determined by GC-MS. Cell viability was used to detect cytotoxic activity. Mechanism of cell death 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. RESULTS: GC-MS analysis of the essential oil revealed the presence of 51 components. The major components were ß-Caryophyllene, 4(14),11-Eudesmadiene, Aromadendrene oxide-(2) and Phytol. EO inhibited the growth and colony formation ability of A431 and HaCaT cells. EO treatment induced nuclear condensation and loss of membrane integrity, DNA fragmentation, increase in sub-G1 DNA content and increase in intracellular ROS level. Inhibition of intracellular ROS by ascorbic acid and N-acetyl cysteine treatment blocked EO induced apoptosis, revealing that apoptotic activity was by ROS accumulation. EO induced apoptosis was found to be due to the loss of mitochondrial membrane potential (ΔΨm), increase in Bax/Bcl-2 ratio, release of cytochrome c and activation of caspases (cleaved form of caspase-3, caspase-8, caspase-9) and by PARP cleavage. CONCLUSION: The present study revealed cancer chemotherapeutic potential of EO from P. missionis. EO induces cell death through intrinsic (mitochondrial) and extrinsic apoptotic pathway in A431 and HaCaT cells. These results suggest that EO could be used as a potential therapeutic agent for the treatment of skin epidermoid cancer.


Subject(s)
Apoptosis/drug effects , Oils, Volatile/pharmacology , Plant Oils/pharmacology , Rutaceae/chemistry , Azulenes , Carcinoma, Squamous Cell/drug therapy , Caspases/metabolism , Cell Cycle , Cell Line, Tumor , Cell Survival/drug effects , Cytochromes c/metabolism , Humans , Membrane Potential, Mitochondrial/drug effects , Mitochondria/metabolism , Polycyclic Sesquiterpenes , Reactive Oxygen Species/metabolism , Sesquiterpenes , Signal Transduction/drug effects , Spheroids, Cellular
4.
Phytomedicine ; 47: 121-134, 2018 Aug 01.
Article in English | MEDLINE | ID: mdl-30166097

ABSTRACT

BACKGROUND: Pamburus missionis (Wight) Swingle (Rutaceae) is traditionally used in the treatment of swellings, chronic rheumatism, paralysis and puerperal diseases. In a previous study the authors demonstrated apoptotic activity of Pamburus missionis essential oil (EO) on A431 and HaCaT cells. The major components of EO were ß-caryophyllene (25.40%), 4(14),11- eudesmadiene (7.17%), aromadendrene oxide 2 (14.01%) (AO-(2) and phytol (6.88%). PURPOSE OF STUDY: To investigate the role as well as the interactions among EO components inducing apoptosis in A431 and HaCaT cells. METHODS: Isobolographic analysis and combination index methods were used to detect the type of interactions among the essential oil (EO) components. Cell viability was used to detect cytotoxic activity. Mechanism of cell death was studied using Annexin V-FITC/PI binding assay, cell cycle analysis, measurement of MMP and ROS generation by flow cytometry. Expression of apoptosis associated proteins was investigated by western blot. RESULTS: Combination of P. missionis EO components: ß-caryophyllene/ aromadendrene oxide 2 (ß-C/AO-(2)), ß-caryophyllene/phytol (ß-C/P) and aromadendrene oxide 2 /phytol (AO-(2)/P) inhibited growth and colony formation ability of skin epidermoid A431 and precancerous HaCaT cells. Synergistic interaction was observed between ß-C/AO-(2) and ß-C/P combination while AO-(2)/P exhibited an additive effect. Combination of components induced chromatin condensation, phosphatidylserine externalisation, increase in sub-G1 DNA content, cell cycle arrest at G0/G1 phase and intracellular ROS accumulation. Inhibition of intracellular ROS by N-acetyl cysteine treatment blocked apoptosis induced by the combinations. The combinations induced apoptosis in A431 and HaCaT cells mediated by loss of mitochondrial membrane potential (ΔΨm), increase in Bax/Bcl-2 ratio, release of cytosolic cytochrome c and activation of caspases (cleaved form of caspase-3, caspase-8, caspase-9) and by PARP cleavage. CONCLUSION: The present study demonstrates interactions among ß-C, AO-(2) and P in the induction of apoptosis on A431 and HaCaT cells. These data suggest the combination of ß-caryophyllene with aromadendrene oxide 2 and phytol could be potential therapeutics for the treatment of skin epidermoid cancer and precancerous cells.


Subject(s)
Apoptosis/drug effects , Azulenes/pharmacology , Keratinocytes/drug effects , Phytol/pharmacology , Sesquiterpenes/pharmacology , Carcinoma, Squamous Cell , Caspases/metabolism , Cell Cycle Checkpoints , Cell Survival/drug effects , Cytochromes c/metabolism , Humans , Membrane Potential, Mitochondrial/drug effects , Oils, Volatile/pharmacology , Polycyclic Sesquiterpenes , Reactive Oxygen Species/metabolism , Rutaceae/chemistry
5.
Life Sci ; 197: 19-29, 2018 Mar 15.
Article in English | MEDLINE | ID: mdl-29407546

ABSTRACT

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.


Subject(s)
Apoptosis/drug effects , Carcinoma, Squamous Cell/drug therapy , Mitochondria/metabolism , Reactive Oxygen Species/metabolism , Sesquiterpenes/pharmacology , Skin Neoplasms/drug therapy , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Survival/drug effects , Humans , Mitochondria/pathology , Sesquiterpenes, Guaiane , Skin Neoplasms/metabolism , Skin Neoplasms/pathology
6.
J Ethnopharmacol ; 124(1): 151-3, 2009 Jul 06.
Article in English | MEDLINE | ID: mdl-19375495

ABSTRACT

AIM OF THE STUDY: The aerial parts of Pamburus missionis (Wight) Swingle (Rutaceae) are traditionally used in the treatment of swelling, chronic rheumatism, paralysis, and puerperal diseases.The aim of this work was to investigate the chemical composition and antibacterial activity of essential oil of Pamburus missionis against different bacterial strains. MATERIALS AND METHODS: The essential oil was obtained from fresh leaves by hydro distillation method and its chemical composition was analyzed by GC and GC-MS. The antibacterial activity was determined by disc diffusion and micro broth dilution assay. RESULTS: GC-MS analysis of the essential oil revealed the presence of 1-tridecanol (38.4%), n-hexadecanoic acid (16.1%), oxygenated monoterpenes (14.4%), monoterpene hydrocarbons (3.1%) and eugenol (1.9%) as the major components. The oil exhibited antibacterial activity at 100 and 450 microg against the test organisms with inhibition zones of 7-25 mm and minimal inhibitory concentrations values in the range of 10-100 and >100 mg/ml. CONCLUSION: The present study reveals the antibacterial potency of essential oil of Pamburus missionis. The use of Pamburus missionis in the treatment of various ailments and puerperal diseases can be attributed to its antibacterial property.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Oils, Volatile/pharmacology , Plant Extracts/pharmacology , Rutaceae/chemistry , Anti-Bacterial Agents/analysis , Eugenol/analysis , Eugenol/pharmacology , Fatty Alcohols/analysis , Fatty Alcohols/pharmacology , Monoterpenes/analysis , Monoterpenes/pharmacology , Oils, Volatile/analysis , Palmitic Acid/analysis , Palmitic Acid/pharmacology , Plant Extracts/analysis , Plant Extracts/chemistry , Plant Leaves
7.
Indian J Pharmacol ; 41(5): 233-6, 2009 Oct.
Article in English | MEDLINE | ID: mdl-20177496

ABSTRACT

OBJECTIVE: To evaluate the antibacterial and antioxidant activity of methanol extract of Evolvulus nummularius (L) L. MATERIALS AND METHODS: Disc diffusion and broth serial dilution tests were used to determine the antibacterial activity of the methanol extract against two Gram-positive bacterial strains (Bacillus subtilus NCIM 2718, Staphylococcus aureus ATCC 25923) and three Gram-negative bacterial strains (Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 70063 and Escherichia coli ATCC 25922). The methanol extract was subjected to preliminary phytochemical analysis. Free radical scavenging activity of the methanol extract at different concentrations was determined with 2, 2-diphenyl-1picrylhydrazyl (DPPH). RESULTS: The susceptible organisms to the methanol extract were Escherichia coli (MIC=12.50 mg/ml) and Bacillus subtilus (MIC=3.125 mg/ml) and the most resistant strains were Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa. The methanol extracts exhibited radical scavenging activity with IC50 of 350 mug/ml. CONCLUSION: The results from the study show that methanol extract of E.nummularius has antibacterial activity. The antioxidant activity may be attributed to the presence of tannins, flavonoids and triterpenoids in the methanol extract. The antibacterial and antioxidant activity exhibited by the methanol extract can be corroborated to the usage of this plant in Indian folk medicine.

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