br Conclusion br Experimental br Background Cancer is

Conclusion
Experimental
Background Cancer is perhaps the most progressive and devastating disease posing a threat of mortality to the entire world despite significant advances in medical technology for its diagnosis and treatment. Recently, wide arrays of phenolic substances, particularly those present in dietary and medicinal plants, have been reported to possess substantial anticarcinogenic and antimutagenic effects [1–10]. Curcumin (Fig. 1), the active ingredient from the spice turmeric (Curcuma longa), is a potent antioxidant [11–14]. The potent antioxidant activity of curcumin and its analogs have received remarkable current interest as they have a unique conjugated structures which show a typical radical trapping ability as a chain-breaking antioxidant [15–19]. The chemopreventive effects of curcumin have been attributed to various biological properties [5,21–23]. Furthermore, curcumin exhibited remarkable cytotoxic effects on various cancer AICAR manufacturer [24] and induced apoptotic cell death in human promyelocytic leukemia HL-60 cells and Human oral squamous carcinoma HSC-4 cells [16]. It has been reported that curcumin was found to decrease the Ehrlich\'s ascites carcinoma (EAC) cell number [25]. Probing further, curcumin is causing tumor cell death by the up-regulation of the proto-oncoprotein Bax, release of cytochrome c from the mitochondria, and activation of caspase-3 [26]. Also, curcumin is bypassing the Bcl-2 checkpoint and overriding its protective effect on apoptosis [27]. Moreover, therapeutic potential of curcumin in human prostate cancer was determined as well as curcumin induction of apoptosis in both androgen-dependent and androgen-independent prostate cancer cells [27–29]. Also, the inhibitory action of a B-diketone analog of curcumin on 7, 12-dimethylbenz[2]anthracene-induced mammary tumorigenesis was detected [30]. In addition, Curcumin derivatives showed potent inhibition of endothelial cell proliferation of MCF-7 human breast tumor cells [31]. In a continuing search for potent and selective cytotoxic antitumor agents, in this work, the followings were done:
Results and discussion
Histopathological results
Conclusion Curcumin (1) and curcumin analogs (2,3) were synthesized and the preclinical safety evaluation in mice and rats were done. Besides, the chemoprotective and chemopreventive effects in DMH-induced colon cancer in albino rats model were performed. The sections of the mammary gland, heart, kidney, liver, spleen, and colon all showed normal structure after 4 weeks treatment, identical of that in 2 weeks treatment by compound 1 (curcumin) and compound 2 (ethyl curcumin). Compound 3 shows some intra-alveolar lung haemorhage. The chemoprotective effects (two weeks prior to the induction of DMH), showed that compound (1) revealed partial protection. Crowding cells at the surface with enlarged hyperchromatic nucleus and scattered aberrant crypt foci were seen. In compound (2), partial protection was seen. Crowding of cells at the surface with enlarged, hyperchromatic nuclei were observed. Scattered aberrant crypt foci were evident. In compound (3), (two weeks prior to the induction of DMH), a moderate protection is evident. Administration of the prophylactic treatment for four weeks before the induction of cancer by DMH, showed that in compound (1), some areas of epithelial surface revealed cell crowding with mitotic nuclear changes and few number of scattered aberrant crypt foci. In compound (2) Group G, better protection was clear. In compound (3), most areas of the colonic tissues showed no signs of neoplastic changes, with the exception of very few areas with crowding cells at the surface; no aberrant crypt foci were present. No adenomatous polyps were seen in all groups. Chemopreventive treatment with curcumin and curcumin analogs for 2 and 4 weeks caused a reduction in the number of aberrant crypt foci (ACF) in each of these groups, compared with ACF number in DMH control group. Compound (3) showed complete inhibition in ACF. Chemopreventive treatment with curcumin and curcumin analogs for 2 and 4 weeks caused a reduction in the number of tumors in each of these groups, compared with tumor number in DMH control group. Compound (3) showed a complete inhibition in the number of tumors.