Insights into the Role of Defective Apoptosis in Cancer Pathogenesis and Therapy

One form of programmed cell death (PCD) is apoptosis. Defective apoptosis is an indispensable causative factor in the development of cancer that allows cancer cells to survive longer and favors the accumulation of oncogenic mutations. Further, upregulation of antiapoptotic proteins (e.g., Bcl-2, Mcl-1) and loss of pro-apoptotic proteins (e.g., Bid, Bad, Bax, Bak) strongly favors apoptosis evasion. The ability of cancer cells to evade apoptosis is critical for the progression and clonal expansion of malignantly transformed cells. Defective apoptosis imparts proliferative advantage to cancer cells or cells with the potential to become cancerous. The mechanisms employed by cancer cells to evade apoptosis can be used in the strategic design of therapeutic regimens aimed at exploiting apoptotic signaling networks to ensure tumor-specific cell death. Therefore, to ensure tumor-specific cell death, we may need to exploit the expression and/or function of different components of apoptotic signaling that are critical for maintaining cell survival and are regulated differently in tumor cells than normal cells. Both inhibitors of anti-apoptotic proteins and activators of pro-apoptotic proteins can be used for cancer therapy. In this chapter, we attempted to summarize the knowledge about the molecular mechanisms of defective apoptosis that could be translated into the development of novel therapeutic agents and therapeutic modalities for cancer treatment

Synthesis and Spectroscopic and Biological Activities of Zn(II) Porphyrin with Oxygen Donors

Results of investigation of the physicochemical properties of zinc complexes containing substituted phenols as axial ligand having general formula [X-Zn-t(p-CH3) PP] [where X = different phenolates as axial ligand] in impurity-free organic solvent are presented. The four-coordinated zinc porphyrin accepts one axial ligand in 1 : 1 molar ratio to form five-coordinated complex, which is purified by column chromatography and characterized by physicochemical, biological evaluation and TGA/DTA studies. Absorption spectra show two principal effects: a red shift for phenols bearing substituted electron releasing groups (−CH3, −NH2) and blue shift for phenols bearing electron withdrawing groups (−NO2, −Cl) relative to Zn-t(p-CH3) PP, respectively. 1H NMR spectra show that the protons of the phenol ring axially attached to the central metal ion are merged with the protons of the porphyrin ring. Fluorescence spectra show two fluorescence peaks in the red region with emission ranging from 550 nm to 700 nm. IR spectra confirm the appearance of Zn-NPor and Zn-O vibrational frequencies, respectively. According to the thermal studies, the complexes have a higher thermal stability and the decomposition temperature of these complexes depends on the axial ligation. The respective complexes of X-ZnII-t(p-CH3) PP were found to possess higher antifungal activity (up to 90%) and higher in vitro cytotoxicity against human cancer cells lines

Cancer Chemoprevention and Piperine: Molecular Mechanisms and Therapeutic Opportunities

Cancer is a genetic disease characterized by unregulated growth and dissemination of malignantly transformed neoplastic cells. The process of cancer development goes through several stages of biochemical and genetic alterations in a target cell. Several dietary alkaloids have been found to inhibit the molecular events and signaling pathways associated with various stages of cancer development and therefore are useful in cancer chemoprevention. Cancer chemoprevention has long been recognized as an important prophylactic strategy to reduce the burden of cancer on health care system. Cancer chemoprevention assumes the use of one or more pharmacologically active agents to block, suppress, prevent, or reverse the development of invasive cancer. Piperine is an active alkaloid with an excellent spectrum of therapeutic activities such as anti-oxidant, anti-inflammatory, immunomodulatory, anti-asthmatic, anti-convulsant, anti-mutagenic, antimycobacterial, anti-amoebic, and anti-cancer activities. In this article, we made an attempt to sum up the current knowledge on piperine that supports the chemopreventive potential of this dietary phytochemical. Many mechanisms have been purported to understand the chemopreventive action of piperine. Piperine has been reported to inhibit the proliferation and survival of many types of cancer cells through its influence on activation of apoptotic signaling and inhibition of cell cycle progression. Piperine is known to affect cancer cells in variety of other ways such as influencing the redox homeostasis, inhibiting cancer stem cell (CSC) self-renewal and modulation of ER stress and autophagy. Piperine can modify activity of many enzymes and transcription factors to inhibit invasion, metastasis, and angiogenesis. Piperine is a potent inhibitor of p-glycoprotein (P-gp) and has a significant effect on the drug metabolizing enzyme (DME) system. Because of its inhibitory influence on P-gp activity, piperine can reverse multidrug resistance (MDR) in cancer cells and acts as bioavailability enhancer for many chemotherapeutic agents. In this article, we emphasize the potential of piperine as a promising cancer chemopreventive agent and the knowledge we collected in this review can be applied in the strategic design of future researches particularly human intervention trials with piperine

<span style="font-size:11.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB">Anti-proliferative effect of leaf extracts of<i style="mso-bidi-font-style: normal"> Eucalyptus citriodora</i> against human cancer cells <i style="mso-bidi-font-style:normal">in vitro</i> and <i style="mso-bidi-font-style: normal">in vivo</i></span>

451-457<span style="font-size:11.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-gb;mso-fareast-language:en-us;mso-bidi-language:="" hi"="" lang="EN-GB">Six different extracts from Eucalyptus citriodora leaves were investigated for their anticancer effect. Extracts were prepared using a range of polar and non-polar solvents to leach out maximum active components. Phytochemical analysis of the extracts revealed the presence of anthraquinones, cardiac glycosides, flavonoids, saponins and tannins. Cytotoxic activity of different extracts was tested in vitro against seven human cancer cell lines from seven different tissues, such as SW-620 (colon), HOP-62 (lung), PC-3 (prostate), OVCAR-5 (ovary), HeLa (cervix), IMR-32 (neuroblastoma) and HEP-2 (liver). The ethyl acetate, chloroform and 50% methanolic extract displayed highest anti-proliferative effect in a dose-dependent manner. In vivo anti-tumor activity was evaluated against murine tumor (solid) model of <span style="mso-bidi-font-style: italic">Ehrlich ascites carcinoma and Sarcoma 180. The results showed that <span style="font-size:11.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-gb;mso-fareast-language:en-us;mso-bidi-language:="" hi"="" lang="EN-GB">ethyl acetate and aqueous<span style="font-size:11.0pt; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-bidi-font-family:mangal;mso-ansi-language:en-in;mso-fareast-language:en-in;="" mso-bidi-language:hi"="" lang="EN-GB"> extracts suppressed the growth of Ehrlich ascites carcinoma (29.79% and 18<span style="mso-bidi-font-style: italic">.48%, respectively), but showed little growth inhibition in case of Sarcoma 180 (13. 86% and 8.57%,<span style="mso-bidi-font-style: italic"> respectively).<span style="font-size:11.0pt; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-bidi-font-family:mangal;mso-ansi-language:en-in;mso-fareast-language:en-in;="" mso-bidi-language:hi"="" lang="EN-GB"> <span style="font-size:11.0pt; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-bidi-font-family:mangal;mso-ansi-language:en-gb;mso-fareast-language:en-us;="" mso-bidi-language:hi"="" lang="EN-GB">The activity might be due to the flavonoids, tannins and saponins that are present in all the extracts of the plant. Further investigation is required for the isolation of active principle(s) from the ethyl acetate extract, which<span style="font-size:11.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi;mso-bidi-font-style:italic"=""> has shown significant <span style="font-size:11.0pt; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-bidi-font-family:mangal;mso-ansi-language:en-gb;mso-fareast-language:en-us;="" mso-bidi-language:hi"="" lang="EN-GB">in vitro<span style="font-size: 11.0pt;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-bidi-font-family:mangal;mso-ansi-language:en-gb;mso-fareast-language:en-us;="" mso-bidi-language:hi"="" lang="EN-GB"> and in vivo anticancer potential.</span

GC–MS analysis of essential oil of <em>Pinus roxburghii</em> Sarg. (Chir pine) needles and evaluation of antibacterial and anti-proliferative properties

34-38The present study was carried out to analyse the biological properties and chemical composition by GC-MS analysis of the essential oil of the needles of Pinus roxburghii. Sixteen components were identified from their fragmentation pattern in the essential oil. Major component present in the essential oil belonged to monoterpene (84.38 %), oxygenated monoterpene (4.23 %) and Sesquiterperne (11.35 %) category. The antibacterial potential was analysed by paper disc diffusion assay against 5 gram-positive bacteria and 5 gram-negative bacteria. Oil showed a broad spectrum of activity by inhibiting all the 5 gram-positive bacteria and 2 gram-negative bacteria viz., Escherichia coli and Campylobacter coli. The antiproliferative property was measured against A-549 (lung), T98G (glioblastoma), PC-3 (prostate) and T47D (breast) human cancer cell lines by Sulphorhodamine-B assay. Here, the essential oil exhibited cytotoxic properties against human cancer cell lines with IC50 values of 161.30 μg/mL and 154.30 μg/mL for A549 and T98G respectively. The results suggest that active component of the essential oil of Pinus roxburghii possess antimicrobial and antiproliferative properties which may be useful for food preservation, pharmaceutical treatment and natural therapies

Antioxidant Activity of Essential Oil and Extracts of Valeriana jatamansi Roots

Valeriana jatamansi is an indigenous medicinal plant used in the treatment of a number of diseases. In the present study, chemical composition of the essential oil was determined by GC-MS. Seven major components were identified in Valeriana jatamansi essential oil, namely, β-vatirenene, β-patchoulene, dehydroaromadendrene, β-gurjunene, patchoulic alcohol, β-guaiene, and α-muurolene. Methanolic, aqueous, and chloroform extracts of Valeriana jatamansi roots were also prepared and analyzed for their polyphenols and flavonoid content. Antioxidant activity of essential oil and different extracts of Valeriana jatamansi roots was determined by DPPH radical scavenging and chelation power assay. A linear correlation has been obtained by comparing the antioxidant activity and polyphenols and flavonoid content of the extracts. Results indicated that antioxidant activity of methanolic extract could be attributed to the presence of rich amount of polyphenols and flavonoid. Essential oil of Valeriana jatamansi roots showed moderate antioxidant activity

Antioxidant activity of essential oil and extracts of Valeriana jatamansiroots,”

Valeriana jatamansi is an indigenous medicinal plant used in the treatment of a number of diseases. In the present study, chemical composition of the essential oil was determined by GC-MS. Seven major components were identified in Valeriana jatamansi essential oil, namely, -vatirenene, -patchoulene, dehydroaromadendrene, -gurjunene, patchoulic alcohol, -guaiene, andmuurolene. Methanolic, aqueous, and chloroform extracts of Valeriana jatamansi roots were also prepared and analyzed for their polyphenols and flavonoid content. Antioxidant activity of essential oil and different extracts of Valeriana jatamansi roots was determined by DPPH radical scavenging and chelation power assay. A linear correlation has been obtained by comparing the antioxidant activity and polyphenols and flavonoid content of the extracts. Results indicated that antioxidant activity of methanolic extract could be attributed to the presence of rich amount of polyphenols and flavonoid. Essential oil of Valeriana jatamansi roots showed moderate antioxidant activity