Author(s): Srivastava P, Yadav N, Lella R,Schneider A, Jones A, et al.
Azadirachta indica, commonly known as neem, has a wide range of medicinal properties. Neem extracts and its purified products have been examined for induction of apoptosis in multiple cancer cell types; however, its underlying mechanisms remain undefined. We show that neem oil (i.e., neem), which contains majority of neem limonoids including azadirachtin, induced apoptotic and autophagic cell death. Gene silencing demonstrated that caspase cascade was initiated by the activation of caspase-9, whereas caspase-8 was also activated late during neem-induced apoptosis. Pretreatment of cancer cells with pan caspase inhibitor, z-VAD inhibited activities of both initiator caspases (e.g., caspase-8 and -9) and executioner caspase-3. Neem induced the release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, suggesting the involvement of both caspase-dependent and AIF-mediated apoptosis. p21 deficiency caused an increase in caspase activities at lower doses of neem, whereas p53 deficiency did not modulate neem-induced caspase activation. Additionally, neem treatment resulted in the accumulation of LC3-II in cancer cells, suggesting the involvement of autophagy in neem-induced cancer cell death. Low doses of autophagy inhibitors (i.e., 3-methyladenine and LY294002) did not prevent accumulation of neem-induced LC3-II in cancer cells. Silencing of ATG5 or Beclin-1 further enhanced neem-induced cell death. Phosphoinositide 3-kinase (PI3K) or autophagy inhibitors increased neem-induced caspase-3 activation and inhibition of caspases enhanced neem-induced autophagy. Together, for the first time, we demonstrate that neem induces caspase-dependent and AIF-mediated apoptosis, and autophagy in cancer cells.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/22915764
Author(s): Takiar R, Nadayil D, Nandakumar A
Author(s): GM Cragg, DJ Newman
Author(s): Kumar S, Suresh PK, Vijayababu MR, Arunkumar A, Arunakaran J
Author(s): R Baral, Chattopadhyay U ( 2004) Neem (Azadirachtaindica) leaf mediated immune activation causes prophylactic growth inhibition of murine Ehrlich carcinoma and B16 melanoma
Author(s): Udeinya IJ,Shu EN, Quakyi I,Ajayi FO
Author(s): Othman F, Motalleb G,Peng SLT,Rahmat A, Fakurazi S, et al.
Author(s): Kavitha K, Priyadarsini RV, Anitha P, Ramalingam K,Sakthivel R, et al.
Author(s): Elumalai P, Gunadharini DN,Senthilkumar K, Banudevi S,Arunkumar R, et al.
Author(s): Sharma C, Andrea J, Goala P, Taher MG,Tahir AR, et al.
Author(s): Dale PS, Tamhankar CP, George D, Daftary GV ( 2001) Co-medication with hydrolytic enzymes in radiation therapy of uterine cervix: evidence of the reduction of acute side effects
Author(s): Popiela T, Kulig J, Hanisch J, Bock PR
Author(s): Tong-PengXu, HuaShen, Ling-Xiang Liu, Yong-QianShu
Author(s): Hsu YL, Cho CY, Kuo PL
Author(s): Kawiak A, Zawacka-Pankau J, Lojkowska E
Author(s): Liu X, Cai W, Niu M, Chong Y, Liu H, et al.
Author(s): Santosh KS, Haruyo I, Gautam S, Ahn-Kwang-Seok, Bharat BA
Author(s): Chen CA, Chang HH, Kao CY, Tsai TH, Chen YJ
Author(s): Prashar R, Kumar A, Banerjee S,Rao AR
Author(s): Prashar R, Kumar A, Hewer A, Cole KJ, Davis W
Author(s): Aruna K,Sivaramakrishnan VM
Author(s): Aruna K, Sivaramakrishnan VM
Author(s): Ganasoundari A, Uma Devi P,Rao BS
Author(s): Leyon PV, Kuttan G
Author(s): Singh N, Singh SM, Shrivastava P
Author(s): Singh SM, Singh N, Shrivastava P
Author(s): Kuo CL, Chou CC, Yung BY
Author(s): Ali H, Dixit S
Author(s): Pahadiya S, Sharma J
Author(s): Ueda JY, Tezuka Y, Banskota AH, Le Tran Q, Tran QK, et al.
Author(s): Wang S, Zheng Z, Weng Y, Yu Y, Zhang D, et al.
Author(s): Renault JH, Nuzillard JM, Le CrouÃ©rour G, ThÃ©penier P, ZÃ¨ches-Hanrot M, et al.